An Examination of Psychotropic Medication Side Effects: Does taking a greater number of psychotropic medications from different classes affect presentation of side effects in adults with ID?

This study examined whether the number of psychotropic medications an individual is taking across classes influences side effects among adults with Intellectual Disability (ID). Participants were 80 adults diagnosed with ID. Dependent variables were the composite score and domain scores of the Matson Evaluation of Drug Side-effects (MEDS), which is an instrument used to assess side effects. There were three levels of the independent variable: Group 1 – those taking zero psychotropic medications, Group 2 – those taking one psychotropic medication, and Group 3 – those taking two psychotropic medications across different medication classes. There was a significant main effect regarding number of psychotropic medication classes prescribed. Further analysis revealed that four of the nine MEDS domains had significantly different mean scores for number of psychotropic medication classes. For the majority of MEDS domains, such as Central Nervous System-General, Parkinsonism/Dyskinesia, and Behavioral/Akathesia domains, participants in the no psychotropic medication group had significantly lower mean scores than those in the one and two psychotropic medication groups. Only two MEDS domains, Cardiovascular and Hematologic Effects as well as Skin, Allergies, and Temperature, were significantly different between participants taking one psychotropic medication as compared with two psychotropic medications from different classes. Implications of these findings and recommendations for future research are discussed.     

Prior immunity helps to explain wave-like behaviour of pandemic influenza in 1918-9

Background

The ecology of influenza may be more complex than is usually assumed. For example, despite multiple waves in the influenza pandemic of 1918-19, many people in urban locations were apparently unaffected. Were they unexposed, or protected by pre-existing cross-immunity in the first wave, by acquired immunity in later waves, or were their infections asymptomatic?

Methods

We modelled all these possibilities to estimate parameters to best explain patterns of repeat attacks in 24,706 individuals potentially exposed to summer, autumn and winter waves in 12 English populations during the 1918-9 pandemic.

Results

Before the summer wave, we estimated that only 52% of persons (95% credibility estimates 41-66%) were susceptible, with the remainder protected by prior immunity. Most people were exposed, as virus transmissibility was high with R₀ credibility estimates of 3.10-6.74. Because of prior immunity, estimates of effective R at the start of the summer wave were lower at 1.57-3.96. Only 25-66% of exposed and susceptible persons reported symptoms. After each wave, 33-65% of protected persons became susceptible again before the next wave through waning immunity or antigenic drift. Estimated rates of prior immunity were less in younger populations (19-59%) than in adult populations (38-66%), and tended to lapse more frequently in the young (49-92%) than in adults (34-76%).

Conclusions

Our model for pandemic influenza in 1918-9 suggests that pre-existing immune protection, presumably induced by prior exposure to seasonal influenza, may have limited the pandemic attack-rate in urban populations, while the waning of that protection likely contributed to recurrence of pandemic waves in exposed cities. In contrast, in isolated populations, pandemic attack rates in 1918-9 were much higher than in cities, presumably because prior immunity was less in populations with infrequent prior exposure to seasonal influenza. Although these conclusions cannot be verified by direct measurements of historical immune mechanisms, our modelling inferences from 1918-9 suggest that the spread of the influenza A (H1N1) 2009 pandemic has also been limited by immunity from prior exposure to seasonal influenza. Components of that immunity, which are measurable, may be short-lived, and not necessarily correlated with levels of HI antibody.

     

Virological fitness of HIV in patients with resistance to enfuvirtide

Resistance to the HIV fusion inhibitor enfuvirtide is associated with mutations in the first heptad repeat region of gp41, but little is known of their impact on replicative fitness in vivo. We followed seven patients undergoing salvage therapy that included enfuvirtide in order to document the temporal generation of genotypic and phenotypic resistance in parallel with replicative fitness. Resistance to enfuvirtide was not associated with decreased replicative fitness of HIV strains infecting these patients.     

Three-dimensional isotropic wavelets for post-acquisitional extraction of latent images of atherosclerotic plaque components from micro-computed tomography of human coronary arteries

RATIONALE AND OBJECTIVES: The capability of wavelet transforms to separate signals into frequency bands is the basis for its use in image compression and storage, data management and transmission, and, recently, extraction of latent images of tissue components from noisy medical images. Analysis of temporal variations of radiofrequency backscatter of intravascular ultrasound with one-dimensional wavelets can detect lipid-laden plaque in coronary arteries with a sensitivity and specificity of >80%. In this study we evaluate the capability of a novel, 3-dimensional isotropic wavelet analysis to perform high resolution, non-directionally biased, statistically reliable, non-invasive discrimination between components of human coronary atherosclerotic plaques in micro-CT. MATERIALS AND METHODS: Coronary artery segments (5-15 mm) were excised at necropsy from 18 individuals with advanced coronary atherosclerosis. Specimens were imaged using a GE Locus SP ex vivo micro-CT scanner and processed for histological correlation (833 sections). The isotropic wavelet constructs were applied to the entire volume of CT data of each arterial segment to distinguish tissue textures of varying scales and intensities. Voxels were classified and plaque characterization achieved by comparing the relative magnitudes of these wavelet constituents to that of several reference plaque tissue components. RESULTS: Processing of micro-CT images via these isotropic wavelet algorithms permitted 3-D, color-coded, high resolution, digital discrimination between lumen, calcific deposits, lipid-rich deposits, and fibromuscular tissue providing detail not possible with conventional thresholding based on Hounsfield intensity units. Using the isotropic wavelets (with histology as the gold standard), lipid-rich pools approaching the size of the filter for the isotropic wavelet algorithm (0.25 mm [250 microns] in length) were identified with 81% sensitivity and 86% specificity. Calcific deposits, fibromuscular tissue, and lumen equal to or larger than the wavelet filter size were detected without error (100% sensitivity and specificity). CONCLUSION: Isotropic wavelet analysis permits high resolution, multi-dimensional identification of coronary atherosclerotic plaque components in micro-CT with sensitivity and specificity similar to that achieved with data obtained invasively (from IVUS in vivo) using one-dimensional wavelets. Further studies are necessary to test the applicability of this technology to clinical, multi-detector scanners.     

Formation of a human-derived fat tissue layer in PdlLGA hollow fibre scaffolds for adipocyte tissue engineering

Development of adipose tissue-engineering strategies, where human bone marrow stromal cells (HBMSC) are combined with three-dimensional scaffolds, is likely to prove valuable for soft tissue restoration. In this study, we assessed the function of poly(dl-lactide-co-glycolide) (P_dlLGA) hollow fibres in facilitating the development of HBMSC-derived adipocytes for advancement of an associated adipocyte layer. The large surface area of 75:25 P_dlLGA fibres facilitated the rapid generation of extensive adipocyte aggregates from an undifferentiated HBMSC monolayer, where the fat-laden cells stained positive with Oil Red O and expressed the adipocyte marker, fatty acid binding protein 3 (FABP3). Following implantation subcutaneously in severely compromised immunodeficient mice, the adipogenic phenotype of the PLGA–adipocyte graft was maintained for up to 56 days. Confocal microscopy showed associated LipidTOX? Deep Red neutral lipid staining in an ^FLP_dlLGA fibre–adipocyte graft after 56 days, critical evidence demonstrating maintenance of the adipocyte phenotype in the subcutaneous graft. To support adipose tissue advancement in a defined volume, the P_dlLGA–adipocyte scaffold was encapsulated within alginate/chitosan hydrogel capsules (typical diameters, 4.0 mm). In a 28-day in vivo trial in immunodeficient mice, clusters of the capsules were maintained at the subcutaneous site. An adipocyte tissue layer advancing within the surrounding hydrogel was demonstrated.     

False-belief understanding in frontotemporal dementia and Alzheimer's disease

The ability to understand other people's behavior in terms of mental states, such as beliefs, desires, and intentions, is central to social interaction. It has been argued that the interpersonal problems of patients with behavioral variant of frontotemporal dementia (FTD-b) are due to a dysfunction of that system. We used first- and second-order false-belief tasks to assess theory-of-mind reasoning in a group of patients with FTD-b and a cognitively matched group of patients with Alzheimer's disease (AD). Both patient groups were equally impaired relative to a healthy elderly group in the cognitively demanding second-order false-belief tasks, revealing that cognitive demands are an important factor in false-belief task performance. Both patient groups reached ceiling performance in the first-order false-belief tasks with minimal cognitive demands, despite the striking difference in their social graces. These results suggest that a conceptual deficit in theory of mind-as measured by the false-belief task-is not at the core of the differences between FTD-b and AD.     

Trauma and Psychosocial Predictors of Substance Abuse in Women Impacted by HIV/AIDS

The purpose of this study was to estimate the relative contributions of trauma, chronic stress burden, depression, anxiety, social support, and social undermining in predicting alcohol and drug abuse, and whether ethnicity moderated these relationships. A multi-ethnic sample of 288 HIV-positive and HIV-negative women was recruited. Multiple group path analysis indicated that greater drug dependence was associated with being HIV+, more depression, and higher chronic burden. Trauma was related only to anxiety. Also, greater alcohol dependence was associated with more depression and more social undermining, and these effects were moderated by ethnicity. African American and Latina women evidenced different relationships between depression, social support and social undermining. Depression, social support and social undermining served as intervening variables in influencing the relationships between the other psychosocial variables and drug and alcohol dependence. The implications of these findings for alcohol and drug abuse research and services are discussed.