Prevalence of primary immune thrombocytopenia in Oklahoma

To determine the prevalence of immune thrombocytopenia (ITP) in Oklahoma regardless of age, clinical characteristics, insurance status, and source of health care. Patients with ITP were identified by the administrative code ICD‐9‐CM 287.3 in Oklahoma hematologists' offices for a 2‐year period, 2003–2004. Prevalence was estimated separately for children (<16 years old) and adults because of their distinct clinical characteristics. Oklahoma census data for 2000 was used as the denominator. Eighty‐seven (94%) of 93 eligible Oklahoma hematologists participated; 620 patients with ITP were identified. The average annual prevalences were as follows: 8.1 (95% CI: 6.7–9.5) per 100,000 children, 12.1 (95% CI: 11.1–13.0) per 100,000 adults, and 11.2 (95% CI: 10.4–12.0) per 100,000 population. Among children and adults less than age 70 years, the prevalence was greater among women. Among adults aged 70 years and older, the prevalence was greater among men. The highest prevalence of ITP was among men age 80 years and older. These data document for the first time the prevalence of ITP regardless of age, clinical characteristics, insurance status, and source of health care. The methodology developed for this prevalence analysis may be adaptable for epidemiologic studies of other uncommon disorders which lack specific diagnostic criteria and are treated primarily by medical specialists. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.     

HIV clades B and C are associated with reduced brain volumetrics

The human immunodeficiency virus (HIV) has multiple genetic clades with varying prevalence throughout the world. Both HIV clade C (HIV-C) and HIV clade B (HIV-B) can cause cognitive impairment, but it is unclear if these clades are characterized by similar patterns of brain dysfunction. We examined brain volumetrics and neuropsychological performance among highly active antiretroviral therapy (HAART)-naïve HIV-B and HIV-C participants. Thirty-four HAART-naïve HIV-infected (HIV+) participants [17 HIV-B (USA); 17 HIV-C (South Africa)] and 34 age- and education-matched HIV-uninfected (HIV?) participants were evaluated. All participants underwent similar laboratory, neuropsychological, and neuroimaging studies. Brain volume measures were assessed within the caudate, putamen, amygdala, thalamus, hippocampus, corpus callosum, and cortical (gray and white matter) structures. A linear model that included HIV status, region, and their interaction assessed the effects of the virus on brain volumetrics. HIV? and HIV+ individuals were similar in age. On laboratory examination, HIV-C participants had lower CD4 cell counts and higher plasma HIV viral loads than HIV-B individuals. In general, HIV+ participants performed significantly worse on neuropsychological measures of processing speed and memory and had significantly smaller relative volumetrics within the thalamus, hippocampus, corpus callosum, and cortical gray and white matter compared to the respective HIV? controls. Both HIV-B and HIV-C are associated with similar volumetric declines when compared to matched HIV? controls. HIV-B and HIV-C were associated with significant reductions in brain volumetrics and poorer neuropsychological performance; however, no specific effect of HIV clade subtype was evident. These findings suggest that HIV-B and HIV-C both detrimentally affect brain integrity.     

Bivalirudin as a Bridge for Anticoagulation in High Risk Neurosurgical Patients with Active DVT or High Risk of Thrombosis

Background

Bivalirudin is an ultrashort acting direct thrombin inhibitor, which has been used in place of heparin in selected settings. We describe our preliminary experience with the use of bivalirudin in patients who required anticoagulation for a deep vein thrombosis, prosthetic heart valve, or hypercoagulable state but were felt to be at high risk for the use of heparin.

Methods

Eight patients in our neurocritical care unit required anticoagulation but were felt to be poor candidates for heparin either due to heparin-induced thrombocytopenia or due to high risk for intracranial hemorrhage. A standard protocol was utilized for bivalirudin with a loading dose of 0.75 mg/kg followed by a continuous infusion of 0.15 mg/kg hr. Serial aPTT levels were checked on a routine basis to monitor therapeutic effect. The bivalirudin infusion was continued for a period of 2 days to 2 weeks prior to starting coumadin therapy.

Results

These patients were in the early postoperative period (within 48 h) following craniotomy, had suffered a recent large hemispheric infarct with hemorrhagic conversion, or had presented with an acute intracerebral hemorrhage. In this small series of patients, no intracranial hemorrhagic complications were encountered. No patients demonstrated progressive systemic thrombotic issues while on bivalirudin.

Conclusion

Based on these findings, bivalirudin may represent a reasonable alternative in patients for whom heparin anticoagulation is contraindicated. A larger multicenter trial of bivalirudin in this setting may be appropriate     

Neuronal fiber bundle lengths in healthy adult carriers of the ApoE4 allele: A quantitative tractography DTI study

The epsilon 4 (e4) isoform of apolipoprotein E (ApoE) is a known genetic risk factor for suboptimal brain health. Morphometry studies of brains with Alzheimer’s disease have reported significant alterations in temporal lobe brain structure of e4 carriers, yet it remains unclear if the presence of an e4 allele is associated with alterations in the microstructure of white matter fiber bundles in healthy populations. The present study used quantitative tractography based on diffusion tensor imaging (qtDTI) to examine the influence of the e4 allele on temporal lobe fiber bundle lengths (FBLs) in 64 healthy older adults with at least one e4 allele (carriers, N?=?23) versus no e4 allele (non-carriers, N?=?41). Subtests from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were also analyzed to examine memory performance between groups. Analyses revealed shorter FBLs in the left uncinate fasciculus (UF) (p?=?.038) of e4 carriers compared to non-carriers. By contrast, neither FBLs specific to the temporal lobe nor memory performances differed significantly between groups. Increased age correlated significantly with shorter FBL in the temporal lobe and UF, and with decreased performance on tests of memory. This is the first study to utilize qtDTI to examine relationships between FBL and ApoE genotype. Results suggest that FBL in the UF is influenced by the presence of an ApoE e4 allele (ApoE4) in healthy older adults. Temporal lobe FBLs, however, are more vulnerable to aging than the presence of an e4 allele.     

Impact of body mass index on neuronal fiber bundle lengths among healthy older adults

Increased body mass index (BMI) has been linked to various detrimental health outcomes, including cognitive dysfunction. Recent work investigating associations between obesity and the brain has revealed decreased white matter microstructural integrity in individuals with elevated BMI, independent of age or comorbid health conditions. However, the relationship between high BMI and white matter fiber bundle length (FBL), which represents a novel metric of microstructural brain integrity, remains unknown. The present study utilized quantitative tractography based on diffusion tensor imaging (DTI) to investigate the relationship between BMI and FBL in 72 otherwise healthy older adults (24 males, 48 females). All participants were between 51 and 85 years of age (M?=?63.26, SD?=?8.76). Results revealed that elevated BMI was associated with shorter FBL in the temporal lobe, independent of age (p?<?.01). In addition, increased age was associated with shorter frontal, temporal, and whole brain FBL (all p values?<?.01). These findings indicate that, while increased age is an important factor associated with reduced FBL, high BMI is uniquely associated with reduced FBL in the temporal lobe. These data offer evidence for additive adverse effects of high BMI on the brain, especially in areas already vulnerable to aging processes and age-related neurodegenerative diseases. Further research is necessary to determine the physiological mechanisms associated with the shortening of FBL in individuals with high BMI.     

Impact of early vs. late childhood early life stress on brain morphometrics

Previous studies of early life trauma suggest that in addition to its emotional impact, exposure to early life stress (ELS) is associated with alterations in brain structure. However, little attention has been devoted to the relationship between emotional processing and brain integrity as a function of age of ELS onset. In the present study we examined whether ELS onset in older ages of youth rather than younger ages is associated with smaller limbic and basal ganglia volumes as measured by magnetic resonance imaging (MRI). We hypothesized that later age of manifestation during youth is associated with smaller volumetric morphology in limbic and basal ganglia volumes in adulthood. A total of 173 individuals were divided into three groups based on the age of self-reported ELS. The three groups included individuals only experiencing early childhood ELS (1 month–7 years, n = 38), those only experiencing later childhood ELS (8 years –17 years, n = 59), and those who have not experienced ELS (n = 76). Anterior cingulate cortex (ACC), hippocampus, amygdala, insula and caudate volumes were measured using a T1-weighted MRI. Analyses confirmed that later childhood ELS was associated with volumetric reductions in the ACC and insula volumes, while ELS experienced between the ages of 1 month and 7 years was not associated with lower brain volumes in these regions. The results may reflect the influence of more fully developed emotional processing of ELS on the developing brain and reinforce a body of research implicating both the ACC and insula in neuropsychiatric disorders and emotional regulation.     

Chapter 3: choosing the important outcomes for a systematic review of a medical test

In this chapter of the Evidence-based Practice Centers Methods Guide for Medical Tests, we describe how the decision to use a medical test generates a broad range of outcomes and that each of these outcomes should be considered for inclusion in a systematic review. Awareness of these varied outcomes affects how a decision maker balances the benefits and risks of the test; therefore, a systematic review should present the evidence on these diverse outcomes. The key outcome categories include clinical management outcomes and direct health effects; emotional, social, cognitive, and behavioral responses to testing; legal and ethical outcomes, and costs. We describe the challenges of incorporating these outcomes in a systematic review, suggest a framework for generating potential outcomes for inclusion, and describe the role of stakeholders in choosing the outcomes for study. Finally, we give examples of systematic reviews that either included a range of outcomes or that might have done so. The following are the key messages in this chapter: Consider both the outcomes that are relevant to the process of testing and those that are relevant to the results of the test. Consider inclusion of outcomes in all five domains: clinical management effects, direct test effects; emotional, social, cognitive and behavioral effects; legal and ethical effects, and costs. Consider to which group the outcomes of testing are most relevant. Given resource limitations, prioritize which outcomes to include. This decision depends on the needs of the stakeholder(s), who should be assisted in prioritizing the outcomes for inclusion.