Prevalence of risk factors for cardiovascular disease in HIV-infected patients over time: the Swiss HIV Cohort Study

OBJECTIVE: Metabolic changes caused by antiretroviral therapy (ART) may increase the risk of coronary heart disease (CHD). We evaluated changes in the prevalence of cardiovascular risk factors (CVRFs) and 10-year risk of CHD in a large cohort of HIV-infected individuals. METHODS: All individuals from the Swiss HIV Cohort Study (SHCS) who completed at least one CVRF questionnaire and for whom laboratory data were available for the period February 2000 to February 2006 were included in the analysis. The presence of a risk factor was determined using cut-offs based on the guidelines of the National Cholesterol Education Program (NCEP ATP III), the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7), the American Diabetes Association, and the Swiss Society for Cardiology. RESULTS: Overall, 8,033 individuals completed at least one CVRF questionnaire. The most common CVRFs in the first completed questionnaire were smoking (57.0%), low high-density lipoprotein (HDL) cholesterol (37.2%), high triglycerides (35.7%), and high blood pressure (26.1%). In total, 2.7 and 13.8% of patients were categorized as being at high (>20%) and moderate (10-20%) 10-year risk for CHD, respectively. Over 6 years the percentage of smokers decreased from 61.4 to 47.6% and the percentage of individuals with total cholesterol >6.2 mmol/L decreased from 21.1 to 12.3%. The prevalence of CVRFs and CHD risk was higher in patients currently on ART than in either pretreated or ART-naive patients. CONCLUSION: During the 6-year observation period, the prevalence of CVRFs remains high in the SHCS. Time trends indicate a decrease in the percentage of smokers and individuals with high cholesterol.

The neurophysiological time pattern of illusionary visual perceptual transitions: a simultaneous EEG and fMRI study

Several divergent cortical mechanisms generating multistability in visual perception have been suggested. Here, we investigated the neurophysiologic time pattern of multistable perceptual changes by means of a simultaneous recording with electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Volunteers responded to the subjective perception of a sudden change between stable patterns of illusionary motion (multistable transition) during a stroboscopic paradigm. We found a global deceleration of the EEG frequency prior to a transition and an occipital-accentuated acceleration after a transition, as obtained by low-resolution electromagnetic tomography analysis (LORETA) analysis. A decrease in BOLD response was found in the prefrontal cortex before, and an increase after the transitions was observed in the right anterior insula, the MT/V5 regions and the SMA. The thalamus and left superior temporal gyrus showed a pattern of decrease before and increase after transitions. No such temporal course was found in the control condition. The multimodal approach of data acquisition allows us to argue that the top-down control of illusionary visual perception depends on selective attention, and that a diminution of vigilance reduces selective attention. These are necessary conditions to allow for the occurrence of a perception discontinuity in absence of a physical change of the stimulus.

Real-time broad-range PCR versus blood culture. A prospective pilot study in pediatric cancer patients with fever and neutropenia

MATERIALS AND METHODS: In a pilot study, results of real-time broad-range (16S rRNA) polymerase chain reaction (PCR) performed on 45 blood samples of pediatric cancer patients with fever and neutropenia were compared with blood culture results. RESULTS: The PCR assay used, having proven a high sensitivity in artificially spiked blood samples, was positive in only three of ten blood culture-positive samples, and it was positive in 10 of 35 (29%) culture-negative samples. CONCLUSION: This broad-range PCR assay, which may identify not-grown bacteria potentially contributing to fever, needs improvement in sensitivity, and different reasons for positive PCR in negative blood culture samples need to be assessed before clinical application.

Real-time visualization of ultrasound-guided retrobulbar blockade: an imaging study

BACKGROUND: /st> Retrobulbar anaesthesia allows eye surgery in awake patients. Severe complications of the blind techniques are reported. Ultrasound-guided needle introduction and direct visualization of the spread of local anaesthetic may improve quality and safety of retrobulbar anaesthesia. Therefore, we developed a new ultrasound-guided technique using human cadavers. METHODS: /st> In total, 20 blocks on both sides in 10 embalmed human cadavers were performed. Using a small curved array transducer and a long-axis approach, a 22 G short bevel needle was introduced under ultrasound guidance lateral and caudal of the eyeball until the needle tip was seen 2 mm away from the optic nerve. At this point, 2 ml of contrast dye as a substitute for local anaesthetic was injected. Immediately after the injection, the spread of the contrast dye was documented by means of CT scans performed in each cadaver. RESULTS: /st> The CT scans showed the distribution of the contrast dye in the muscle cone and behind the posterior sclera in all but one case. No contrast dye was found inside the optic nerve or inside the eyeball. In one case, there could be an additional trace of contrast dye behind the orbita. CONCLUSIONS: /st> Our new ultrasound-guided technique has the potential to improve safety and efficacy of the procedure by direct visualization of the needle placement and the distribution of the injected fluid. Furthermore, the precise injection near the optic nerve could lead to a reduction of the amount of the local anaesthetic needed with fewer related complications.

The effect of naloxone-3-glucuronide on colonic transit time in healthy men after acute morphine administration: a placebo-controlled double-blinded crossover preclinical volunteer study

BACKGROUND: Constipation is a significant side effect of opioid therapy. We have previously demonstrated that naloxone-3-glucuronide (NX3G) antagonizes the motility-lowering-effect of morphine in the rat colon. AIM: To find out whether oral NX3G is able to reduce the morphine-induced delay in colonic transit time (CTT) without being absorbed and influencing the analgesic effect. METHODS: Fifteen male volunteers were included. Pharmacokinetics: after oral administration of 0.16 mg/kg NX3G, blood samples were collected over a 6-h period. Pharmacodynamics: NX3G or placebo was then given at the start time and every 4 h thereafter. Morphine (0.05 mg/kg) or placebo was injected s.c. 2 h after starting and thereafter every 6 h for 24 h. CTT was measured over a 48-h period by scintigraphy. Pressure pain threshold tests were performed. RESULTS: Neither NX3G nor naloxone was detected in the venous blood. The slowest transit time was observed during the morphine phase, which was significantly different from morphine with NX3G and placebo. The pain perception was not significantly influenced by NX3G. CONCLUSIONS: Orally administered NX3G is able to reverse the morphine-induced delay of CTT in humans without being detected in peripheral blood samples. Therefore, NX3G may improve symptoms of constipation in-patients using opioid medication without affecting opioid-analgesic effects.

Time-dependent hierarchical organization of spatial working memory: a transcranial magnetic stimulation study

The performance of memory-guided saccades with two different delays (3 and 30 s of memorization) was studied in seven healthy subjects. Double-pulse transcranial magnetic stimulation (dTMS) with an interstimulus interval of 100 ms was applied over the right dorsolateral prefrontal cortex (DLPFC) early (1 s after target presentation) and late (28 s after target presentation). Early stimulation significantly increased in both delays the percentage of error in amplitude (PEA) of contralateral memory-guided saccades compared to the control experiment without stimulation. dTMS applied late in the delay had no significant effect on PEA. Furthermore, we found a significantly smaller effect of early stimulation in the long-delay paradigm. These results suggest a time-dependent hierarchical organization of the spatial working memory with a functional dominance of DLPFC during the early memorization, independent from the memorization delay. For a long memorization delay, however, working memory seems to have an additional, DLPFC-independent component.

Parameter-free extraction of the functional network topology from intracranial EEG recordings: a time-resolved study of graph properties in focal onset seizures

Rationale: Focal onset epileptic seizures are due to abnormal interactions between distributed brain areas. By estimating the cross-correlation matrix of multi-site intra-cerebral EEG recordings (iEEG), one can quantify these interactions. To assess the topology of the underlying functional network, the binary connectivity matrix has to be derived from the cross-correlation matrix by use of a threshold. Classically, a unique threshold is used that constrains the topology [1]. Our method aims to set the threshold in a data-driven way by separating genuine from random cross-correlation. We compare our approach to the fixed threshold method and study the dynamics of the functional topology. Methods: We investigate the iEEG of patients suffering from focal onset seizures who underwent evaluation for the possibility of surgery. The equal-time cross-correlation matrices are evaluated using a sliding time window. We then compare 3 approaches assessing the corresponding binary networks. For each time window: * Our parameter-free method derives from the cross-correlation strength matrix (CCS)[2]. It aims at disentangling genuine from random correlations (due to finite length and varying frequency content of the signals). In practice, a threshold is evaluated for each pair of channels independently, in a data-driven way. * The fixed mean degree (FMD) uses a unique threshold on the whole connectivity matrix so as to ensure a user defined mean degree. * The varying mean degree (VMD) uses the mean degree of the CCS network to set a unique threshold for the entire connectivity matrix. * Finally, the connectivity (c), connectedness (given by k, the number of disconnected sub-networks), mean global and local efficiencies (Eg, El, resp.) are computed from FMD, CCS, VMD, and their corresponding random and lattice networks. Results: Compared to FMD and VMD, CCS networks present: *topologies that are different in terms of c, k, Eg and El. *from the pre-ictal to the ictal and then post-ictal period, topological features time courses that are more stable within a period, and more contrasted from one period to the next. For CCS, pre-ictal connectivity is low, increases to a high level during the seizure, then decreases at offset. k shows a ‘‘U-curve’’ underlining the synchronization of all electrodes during the seizure. Eg and El time courses fluctuate between the corresponding random and lattice networks values in a reproducible manner. Conclusions: The definition of a data-driven threshold provides new insights into the topology of the epileptic functional networks.

Non-AIDS defining cancers in the D:A:D Study - time trends and predictors of survival: a cohort study

Background Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004–2010, and described subsequent mortality and predictors of these. Methods Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient’s last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient’s death, 1st February 2010 or 6 months after the patient’s last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression. Results Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin’s lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004–2010 in this large observational cohort. Conclusions The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC.

Gender differences in the association of a high quality job and self-esteem over time: A multiwave study

High self-esteem often predicts job-related outcomes, such as high job satisfaction or high status. Theoretically, high quality jobs (HQJs) should be important for self-esteem, as they enable people to use a variety of skills and attribute accomplishments to themselves, but research findings are mixed. We expected reciprocal relationships between self-esteem and HQJ. However, as work often is more important for the status of men, we expected HQJ to have a stronger influence on self-esteem for men as compared to women. Conversely, task-related achievements violate gender stereotypes for women, who may need high self-esteem to obtain HQJs. In a 4-year cross-lagged panel analysis with 325 young workers, self-esteem predicted HQJ; the lagged effect from HQJ on self-esteem was marginally significant. In line with the hypotheses, the multigroup model showed a significant path only from self-esteem to HQJ for women, and from HQJ to self-esteem for men. The reverse effect was not found for women, and only marginally significant for men. Overall, although there were some indications for reciprocal effects, our findings suggest that women need high self-esteem to obtain HQJs to a greater degree than men, and that men base their self-esteem on HQJs to a greater extent than women.