Key reports from the 9th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 2007

The 9th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV provided a forum for the presentation of basic and clinical research focused on the pathogenesis and management of lipodystrophy and other adverse events associated with antiretroviral therapy. New data were reported on the contribution of both antiretroviral therapy and HIV infection itself on the development of metabolic abnormalities in patients with lipodystrophy, including insulin resistance and dyslipidaemia, which are associated with an increased risk of diabetes and cardiovascular disease. In addition, an emerging role of HIV and antiretroviral therapy in bone, liver and kidney disease were highlighted. A major focus of the data presented in these areas concerned the identification and evaluation of risk factors and appropriate surrogate markers for defining cardiovascular disease risk as well as other outcomes of long-term treatment. The complexity of defining such risk factors was underscored by data describing the impact of race, age and gender in the progression of metabolic disease and related complications among different HIV-infected populations. Finally, advances in the development of pharmacovigilance reporting systems in resource-limited settings and their impact upon healthcare policies and the provision of patient care were also described.     

A genetic association study of D-dimer levels with 50 K SNPs from a candidate gene chip in four ethnic groups

Introduction

D-dimer, a fibrin degradation product, is related to risk of cardiovascular disease and venous thromboembolism. Genetic determinants of D-dimer are not well characterized; notably, few data have been reported for African American (AA), Asian, and Hispanic populations.

Materials and Methods

We conducted a large-scale candidate gene association study to identify variants in genes associated with D-dimer levels in multi-ethnic populations. Four cohorts, comprising 6,848 European Americans (EAs), 2,192 AAs, 670 Asians, and 1,286 Hispanics in the National Heart, Lung, and Blood Institute Candidate Gene Association Resource consortium, were assembled. Approximately 50,000 genotyped single nucleotide polymorphisms (SNPs) in 2,000 cardiovascular disease gene loci were analyzed by linear regression, adjusting for age, sex, study site, and principal components in each cohort and ethnic group. Results across studies were combined within each ethnic group by meta-analysis.

Results

Twelve SNPs in coagulation factor V (F5) and 3 SNPs in the fibrinogen alpha chain (FGA) were significantly associated with D-dimer level in EAs with p < 2.0 × 10^− 6. The signal for the most associated SNP in F5 (rs6025, factor V Leiden) was replicated in Hispanics (p = 0.023), while that for the top functional SNP in FGA (rs6050) was replicated in AAs (p = 0.006). No additional SNPs were significantly associated with D-dimer.

Conclusions

Our study replicated previously reported associations of D-dimer with SNPs in F5 and FGA in EAs; we demonstrated replication of the association of D-dimer with FGA rs6050 in AAs and the factor V Leiden variant in Hispanics.     

Differential vulnerability of white matter structures to experimental infantile hydrocephalus detected by diffusion tensor imaging

Purpose

The differential vulnerability of white matter (WM) to acute and chronic infantile hydrocephalus and the related effects of early and late reservoir treatment are unknown, but diffusion tensor imaging (DTI) could provide this information. Thus, we characterized WM integrity using DTI in a clinically relevant model.

Methods

Obstructive hydrocephalus was induced in 2-week-old felines by intracisternal kaolin injection. Ventricular reservoirs were placed 1 (early) or 2 (late) weeks post-kaolin and tapped frequently based solely on neurological deficit. Hydrocephalic and age-matched control animals were sacrificed 12 weeks postreservoir. WM integrity was evaluated in the optic system, corpus callosum, and internal capsule prereservoir and every 3 weeks using DTI. Analyses were grouped as acute (<6 weeks) or chronic (≥6 weeks).

Results

In the corpus callosum during acute stages, fractional anisotropy (FA) decreased significantly with early and late reservoir placement (p?=?0.0008 and 0.0008, respectively), and diffusivity increased significantly in early (axial, radial, and mean diffusivity, p?=?0.0026, 0.0012, and 0.0002, respectively) and late (radial and mean diffusivity, p?=?0.01 and 0.0038, respectively) groups. Chronically, the corpus callosum was thinned and not detectable by DTI. FA was significantly lower in the optic chiasm and tracts (p?=?0.0496 and 0.0052, respectively) with late but not early reservoir placement. In the internal capsule, FA in both reservoir groups increased significantly with age (p?Conclusions All hydrocephalic animals treated with intermittent ventricular reservoir tapping demonstrated progressive ventriculomegaly. Both reservoir groups demonstrated WM integrity loss, with the CC the most vulnerable and the optic system the most resilient.     

Augmentation of spelling therapy with transcranial direct current stimulation in primary progressive aphasia: Preliminary results and challenges

Background: Primary progressive aphasia (PPA) is a neurodegenerative disease that primarily affects language functions and often begins in the fifth or sixth decade of life. The devastating effects on work and family life call for the investigation of treatment alternatives. In this article, we present new data indicating that neuromodulatory treatment, using transcranial direct current stimulation (tDCS) combined with a spelling intervention, shows some promise for maintaining or even improving language, at least temporarily, in PPA.

Aims: The main aim of the present article is to determine whether tDCS plus spelling intervention is more effective than spelling intervention alone in treating written language in PPA. We also asked whether the effects of tDCS are sustained longer than the effects of spelling intervention alone.

Methods & Procedures: We present data from six PPA participants who underwent anodal tDCS or sham plus spelling intervention in a within-subject crossover design. Each stimulation condition lasted 3 weeks or a total of 15 sessions with a 2-month interval in between. Participants were evaluated on treatment tasks as well as on other language and cognitive tasks at 2-week and 2-month follow-up intervals after each stimulation condition.

Outcomes & Results: All participants showed improvement in spelling (with sham or tDCS). There was no difference in the treated items between the two conditions. There was, however, consistent and significant improvement for untrained items only in the tDCS plus spelling intervention condition. Furthermore, the improvement lasted longer in the tDCS plus spelling intervention condition compared to sham plus spelling intervention condition.

Conclusions: Neuromodulation with tDCS offers promise as a means of augmenting language therapy to improve written language function at least temporarily in PPA. The consistent finding of generalisation of treatment benefits to untreated items and the superior sustainability of treatment effects with tDCS justifies further investigations. However, the small sample size still requires caution in interpretation. Present interventions need to be optimised, and particular challenges, such as ways to account for the variable effect of degeneration in each individual, are discussed.     

Muscle activity,cross-sectional area,and density following passive standing and whole body vibration: A case series

Objective

To investigate the effects of intermittent passive standing (PS) and whole body vibration (WBV) on the electromyography (EMG) activity, cross-sectional area, and density of lower extremity muscles in individuals with chronic motor complete spinal cord injury (SCI).

Design

Case series.

Methods

Seven adult men with chronic (≥2 years), thoracic motor complete (AIS A–B) SCI completed a 40-week course of thrice-weekly intermittent PS-WBV therapy, in a flexed knee posture (160°), for 45 minutes per session at a frequency of 45 Hz and 0.6–0.7 mm displacement using the WAVE^® Pro Plate, with an integrated EasyStand™ standing frame. EMG was measured in major lower extremity muscles to represent muscle activity during PS-WBV. The cross-sectional area and density of the calf muscles were measured using peripheral quantitative computed tomography at the widest calf cross-section (66% of the tibia length) at pre- and post-intervention. All measured variables were compared between the pre- and post-intervention measurements to assess change after the PS-WBV intervention.

Results

PS-WBV acutely induced EMG activity in lower extremity muscles of SCI subjects. No significant changes in lower extremity EMG activity, muscle cross-sectional area, or density were observed following the 40-week intervention.

Conclusions

Although acute exposure to PS-WBV can induce electrophysiological activity of lower extremity muscles during PS in men with motor complete SCI, the PS-WBV intervention for 40 weeks was not sufficient to result in enhanced muscle activity, or to increase calf muscle cross-sectional area or density.     

An early intervention programme had no detectable influence on the health status of people with musculoskeletal injuries following road traffic crashes: Comparative study

Objective

To compare the health status of people with minor injuries from road traffic crashes that are exposed to an early, active intervention programme (intervention group) with those receiving usual care (control group) over a 12 month period.

Design

Prospective comparative study using sequential cohorts.

Subjects

People presenting to hospital emergency departments with mild to moderate musculoskeletal injuries following road traffic crashes.

Main outcome measures

Physical Component Score (PCS) and Mental Component Score (MCS) of the Short Form 36 (SF-36) health status measure; Hospital Anxiety and Depression Scale (HADS) and the Functional Rating Index (FRI) recorded immediately post-crash, at 6 months and at 12 months after injury.

Results

There were 95 participants allocated to the control group and 98 allocated to the intervention group. Participants were enrolled at a mean of 9.3 days following the crash. There were no significant differences in baseline health measures between the groups. Apart from a small improvement in anxiety for the intervention group, there were no significant differences in health status between the groups. Twenty percent of participants in the intervention group received treatment from external healthcare providers that was inconsistent with the recommendations of the intervention programme.

Conclusions

The intervention programme failed to result in a clinically significant improvement in health outcomes compared with usual care. There is some evidence to suggest that the intervention had some psychological benefits, as evidenced by the small improvement in anxiety levels. Limited adherence, frequent use of co-interventions, or other factors (such as intervention content or intensity) may have reduced its effect.     

Cross-sectional area of the abdomen predicts complication incidence in patients undergoing sternal reconstruction

Background

Sternal reconstruction with vascularized flaps is central to the management of sternal wound infections and mediastinitis but carries a high risk of complications. There is a need to identify reliable predictors of complication risk to help inform patients and clinicians in preparation for surgery. Unfortunately, body mass index and serum albumin may not be reliable predictors of complication rates. Analytic morphomics provides a robust quantitative method to measure patients' obesity as it pertains to their risk of complications in undergoing sternal reconstruction.

Methods

We identified 34 patients with preoperative computed tomography scans of the abdomen from a cohort of sternal reconstructions performed between 1997 and 2010. Using semiautomated analytic morphomics, we identified the patients' skin and fascia layers between the ninth and 12th thoracic spine levels; from these landmarks, we calculated morphomic measurements of the patients' abdomens, including their total body cross sectional area and the cross sectional area of their subcutaneous fat. We obtained the incidence of complications from chart review and correlated the incidence of complications (including seroma, hematoma, recurrent wounds, mediastinitis, tracheostomy, and death) with patients' morphomic measurements.

Results

Sixty-two percent of patients (n = 21) suffered complications after their operation. Those who suffered from complications, relative to those who did not have complications, had increased visceral fat area (12,547.2 mm²versus 6569.9 mm², P = 0.0080), subcutaneous fat area (16,520.2 mm²versus 8020.1 mm², P = 0.0036), total body area (91,028.6 mm²versus 67,506.5 mm², P = 0.0022), fascia area (69,238.4 mm²versus 56,730.9 mm², P = 0.0118), total body circumference (1101.8 mm versus 950.2 mm, P = 0.0017), and fascia circumference (967.5 mm versus 868.1 mm, P = 0.0077). We also demonstrated a significant positive correlation between the previously mentioned morphomic measurements and the incidence of complications in multivariate logistic regression models, with odds ratios ranging from 1.19–3.10 (P values ranging from 0.010–0.022).

Conclusions

Increases in abdominal morphomic measurements correlate strongly with the incidence of complications in patients undergoing sternal reconstruction. This finding may influence preoperative risk stratification and surgical decision making in this patient population.