Patterns of Adherence to Raltegravir-Based Regimens and the Risk of Virological Failure Among HIV-Infected Patients: The RALTECAPS Cohort Study.

ABSTRACT:: Adherence patterns and their influence on virologic outcome are well characterized for protease inhibitor (PI)- and non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens. We aimed to determine how patterns of adherence to raltegravir influence the risk of virological failure. We conducted a prospective multicenter cohort following 81 HIV-infected antiretroviral-naive or experienced subjects receiving or starting twice-a-day raltegravir-based antiretroviral therapy. Their adherence patterns were monitored using the Medication Events Monitoring System. During follow-up (188 days, ±77), 12 (15%) of 81 subjects experienced virological failure. Longer treatment interruption [adjusted odds ratio per 24-hour increase: 2.4; 95% confidence interval: 1.2 to 6.9; P < 0.02] and average adherence (odds ratio per 5% increase: 0.68; 95% confidence interval: 0.46 to 1.00, P < 0.05) were both independently associated with virological failure controlling for prior duration of viral suppression. Timely interdose intervals and high levels of adherence to raltegravir are both necessary to control HIV replication.

Body fat distribution in white and black women: different patterns of intraabdominal and subcutaneous abdominal adipose tissue utilization with weight loss.

BACKGROUND: Intraabdominal adipose tissue (IAAT) is the body fat depot most strongly related to disease risk. Weight reduction is advocated for overweight people to reduce total body fat and IAAT, although little is known about the effect of weight loss on abdominal fat distribution in different races. OBJECTIVE: We compared the effects of diet-induced weight loss on changes in abdominal fat distribution in white and black women. DESIGN: We studied 23 white and 23 black women, similar in age and body composition, in the overweight state [mean body mass index (BMI; in kg/m(2)): 28.8] and the normal-weight state (mean BMI: 24.0) and 38 never-overweight control women (mean BMI: 23.4). We measured total body fat by using a 4-compartment model, trunk fat by using dual-energy X-ray absorptiometry, and cross-sectional areas of IAAT (at the fourth and fifth lumbar vertebrae) and subcutaneous abdominal adipose tissue (SAAT) by using computed tomography. RESULTS: Weight loss was similar in white and black women (13.1 and 12.6 kg, respectively), as were losses of total fat, trunk fat, and waist circumference. However, white women lost more IAAT (P < 0.001) and less SAAT (P < 0.03) than did black women. Fat patterns regressed toward those of their respective control groups. Changes in waist circumference correlated with changes in IAAT in white women (r = 0.54, P < 0.05) but not in black women (r = 0.19, NS). CONCLUSIONS: Despite comparable decreases in total and trunk fat, white women lost more IAAT and less SAAT than did black women. Waist circumference was not a suitable surrogate marker for tracking changes in the visceral fat compartment in black women.

Changing patterns of cancer incidence in the early- and late-HAART periods: the Swiss HIV Cohort Study.

BACKGROUND: The advent of highly active antiretroviral therapy (HAART) in 1996 led to a decrease in the incidence of Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL), but not of other cancers, among people with HIV or AIDS (PWHA). It also led to marked increases in their life expectancy. METHODS: We conducted a record-linkage study between the Swiss HIV Cohort Study and nine Swiss cantonal cancer registries. In total, 9429 PWHA provided 20,615, 17,690, and 15,410 person-years in the pre-, early-, and late-HAART periods, respectively. Standardised incidence ratios in PWHA vs the general population, as well as age-standardised, and age-specific incidence rates were computed for different periods. RESULTS: Incidence of KS and NHL decreased by several fold between the pre- and early-HAART periods, and additionally declined from the early- to the late-HAART period. Incidence of cancers of the anus, liver, non-melanomatous skin, and Hodgkin's lymphoma increased in the early- compared with the pre-HAART period, but not during the late-HAART period. The incidence of all non-AIDS-defining cancers (NADCs) combined was similar in all periods, and approximately double that in the general population. CONCLUSIONS: Increases in the incidence of selected NADCs after the introduction of HAART were largely accounted for by the ageing of PWHA.

Predicting current and future spatial community patterns of plant functional traits

Community-level patterns of functional traits relate to community assembly and ecosystem functioning. By modelling the changes of different indices describing such patterns - trait means, extremes and diversity in communities - as a function of abiotic gradients, we could understand their drivers and build projections of the impact of global change on the functional components of biodiversity. We used five plant functional traits (vegetative height, specific leaf area, leaf dry matter content, leaf nitrogen content and seed mass) and non-woody vegetation plots to model several indices depicting community-level patterns of functional traits from a set of abiotic environmental variables (topographic, climatic and edaphic) over contrasting environmental conditions in a mountainous landscape. We performed a variation partitioning analysis to assess the relative importance of these variables for predicting patterns of functional traits in communities, and projected the best models under several climate change scenarios to examine future potential changes in vegetation functional properties. Not all indices of trait patterns within communities could be modelled with the same level of accuracy: the models for mean and extreme values of functional traits provided substantially better predictive accuracy than the models calibrated for diversity indices. Topographic and climatic factors were more important predictors of functional trait patterns within communities than edaphic predictors. Overall, model projections forecast an increase in mean vegetation height and in mean specific leaf area following climate warming. This trend was important at mid elevation particularly between 1000 and 2000 m asl. With this study we showed that topographic, climatic and edaphic variables can successfully model descriptors of community-level patterns of plant functional traits such as mean and extreme trait values. However, which factors determine the diversity of functional traits in plant communities remains unclear and requires more investigations.

Impact of the Advisa MRI pacing system on the diagnostic quality of cardiac MR images and contraction patterns of cardiac muscle during scans: Advisa MRI randomized clinical multicenter study results.

BACKGROUND: The Advisa MRI system is designed to safely undergo magnetic resonance imaging (MRI). Its influence on image quality is not well known. OBJECTIVE: To evaluate cardiac magnetic resonance (CMR) image quality and to characterize myocardial contraction patterns by using the Advisa MRI system. METHODS: In this international trial with 35 participating centers, an Advisa MRI system was implanted in 263 patients. Of those, 177 were randomized to the MRI group and 150 underwent MRI scans at the 9-12-week visit. Left ventricular (LV) and right ventricular (RV) cine long-axis steady-state free precession MR images were graded for quality. Signal loss along the implantable pulse generator and leads was measured. The tagging CMR data quality was assessed as the percentage of trackable tagging points on complementary spatial modulation of magnetization acquisitions (n=16) and segmental circumferential fiber shortening was quantified. RESULTS: Of all cine long-axis steady-state free precession acquisitions, 95% of LV and 98% of RV acquisitions were of diagnostic quality, with 84% and 93%, respectively, being of good or excellent quality. Tagging points were trackable from systole into early diastole (360-648 ms after the R-wave) in all segments. During RV pacing, tagging demonstrated a dyssynchronous contraction pattern, which was not observed in nonpaced (n = 4) and right atrial-paced (n = 8) patients. CONCLUSIONS: In the Advisa MRI study, high-quality CMR images for the assessment of cardiac anatomy and function were obtained in most patients with an implantable pacing system. In addition, this study demonstrated the feasibility of acquiring tagging data to study the LV function during pacing.

Transcriptional regulatory patterns of the myelin basic protein and malic enzyme genes by the thyroid hormone receptors alpha1 and beta1.

While there is evidence that the two ubiquitously expressed thyroid hormone (T3) receptors, TRalpha1 and TRbeta1, have distinct functional specificities, the mechanism by which they discriminate potential target genes remains largely unexplained. In this study, we demonstrate that the thyroid hormone response elements (TRE) from the malic enzyme and myelin basic protein genes (METRE and MBPTRE) respectively, are not functionally equivalent. The METRE, which is a direct repeat motif with a 4-base pair gap between the two half-site hexamers binds thyroid hormone receptor as a heterodimer with 9-cis-retinoic acid receptor (RXR) and mediates a high T3-dependent activation in response to TRalpha1 or TRbeta1 in NIH3T3 cells. In contrast, the MBPTRE, which consists of an inverted palindrome formed by two hexamers spaced by 6 base pairs, confers an efficient transactivation by TRbeta1 but a poor transactivation by TRalpha1. While both receptors form heterodimers with RXR on MBPTRE, the poor transactivation by TRalpha1 correlates also with its ability to bind efficiently as a monomer. This monomer, which is only observed with TRalpha1 bound to MBPTRE, interacts neither with N-CoR nor with SRC-1, explaining its functional inefficacy. However, in Xenopus oocytes, in which RXR proteins are not detectable, the transactivation mediated by TRalpha1 and TRbeta1 is equivalent and independent of a RXR supply, raising the question of the identity of the thyroid hormone receptor partner in these cells. Thus, in mammalian cells, the binding characteristics of TRalpha1 to MBPTRE (i.e. high monomer binding efficiency and low transactivation activity) might explain the particular pattern of T3 responsiveness of MBP gene expression during central nervous system development.

Decreasing mortality and changing patterns of causes of death in the Swiss HIV Cohort Study.

BACKGROUND: Mortality among HIV-infected persons is decreasing, and causes of death are changing. Classification of deaths is hampered because of low autopsy rates, frequent deaths outside of hospitals, and shortcomings of International Statistical Classification of Diseases and Related Health Problems (ICD-10) coding. METHODS: We studied mortality among Swiss HIV Cohort Study (SHCS) participants (1988-2010) and causes of death using the Coding Causes of Death in HIV (CoDe) protocol (2005-2009). Furthermore, we linked the SHCS data to the Swiss National Cohort (SNC) cause of death registry. RESULTS: AIDS-related mortality peaked in 1992 [11.0/100 person-years (PY)] and decreased to 0.144/100 PY (2006); non-AIDS-related mortality ranged between 1.74 (1993) and 0.776/100 PY (2006); mortality of unknown cause ranged between 2.33 and 0.206/100 PY. From 2005 to 2009, 459 of 9053 participants (5.1%) died. Underlying causes of deaths were: non-AIDS malignancies [total, 85 (19%) of 446 deceased persons with known hepatitis C virus (HCV) status; HCV-negative persons, 59 (24%); HCV-coinfected persons, 26 (13%)]; AIDS [73 (16%); 50 (21%); 23 (11%)]; liver failure [67 (15%); 12 (5%); 55 (27%)]; non-AIDS infections [42 (9%); 13 (5%); 29 (14%)]; substance use [31 (7%); 9 (4%); 22 (11%)]; suicide [28 (6%); 17 (7%), 11 (6%)]; myocardial infarction [28 (6%); 24 (10%), 4 (2%)]. Characteristics of deceased persons differed in 2005 vs. 2009: median age (45 vs. 49 years, respectively); median CD4 count (257 vs. 321 cells/μL, respectively); the percentage of individuals who were antiretroviral therapy-naïve (13 vs. 5%, respectively); the percentage of deaths that were AIDS-related (23 vs. 9%, respectively); and the percentage of deaths from non-AIDS-related malignancies (13 vs. 24%, respectively). Concordance in the classification of deaths was 72% between CoDe and ICD-10 coding in the SHCS; and 60% between the SHCS and the SNC registry. CONCLUSIONS: Mortality in HIV-positive persons decreased to 1.33/100 PY in 2010. Hepatitis B or C virus coinfections increased the risk of death. Between 2005 and 2009, 84% of deaths were non-AIDS-related. Causes of deaths varied according to data source and coding system.

Anatomical exposure patterns of skin to sunlight: relative contributions of direct, diffuse and reflected ultraviolet radiation

Summary Background  The dose-response between ultraviolet (UV) exposure patterns and skin cancer occurrence is not fully understood. Sun-protection messages often focus on acute exposure, implicitly assuming that direct UV radiation is the key contributor to the overall UV exposure. However, little is known about the relative contribution of the direct, diffuse and reflected radiation components. Objective  To investigate solar UV exposure patterns at different body sites with respect to the relative contribution of the direct, diffuse and reflected radiation. Methods  A three-dimensional numerical model was used to assess exposure doses for various body parts and exposure scenarios of a standing individual (static and dynamic postures). The model was fed with erythemally weighted ground irradiance data for the year 2009 in Payerne, Switzerland. A year-round daily exposure (08:00-17:00 h) without protection was assumed. Results  For most anatomical sites, mean daily doses were high (typically 6·2-14·6 standard erythemal doses) and exceeded the recommended exposure values. Direct exposure was important during specific periods (e.g. midday during summer), but contributed moderately to the annual dose, ranging from 15% to 24% for vertical and horizontal body parts, respectively. Diffuse irradiation explained about 80% of the cumulative annual exposure dose. Acute diffuse exposures were also observed during cloudy summer days. Conclusions  The importance of diffuse UV radiation should not be underestimated when advocating preventive measures. Messages focused on avoiding acute direct exposures may be of limited efficiency to prevent skin cancers associated with chronic exposure.

Comparisons of intensity-duration patterns of physical activity in the US, Jamaica and 3 African countries.

BACKGROUND: This difference in how populations living in low-, middle or upper-income countries accumulate daily PA, i.e. patterns and intensity, is an important part in addressing the global PA movement. We sought to characterize objective PA in 2,500 participants spanning the epidemiologic transition. The Modeling the Epidemiologic Transition Study (METS) is a longitudinal study, in 5 countries. METS seeks to define the association between physical activity (PA), obesity and CVD risk in populations of African origin: Ghana (GH), South Africa (SA), Seychelles (SEY), Jamaica (JA) and the US (suburban Chicago). METHODS: Baseline measurements of objective PA, SES, anthropometrics and body composition, were completed on 2,500 men and women, aged 25-45 years. Moderate and vigorous PA (MVPA, min/d) on week and weekend days was explored ecologically, by adiposity status and manual labor. RESULTS: Among the men, obesity prevalence reflected the level of economic transition and was lowest in GH (1.7%) and SA (4.8%) and highest in the US (41%). SA (55%) and US (65%) women had the highest levels of obesity, compared to only 16% in GH. More men and women in developing countries engaged in manual labor and this was reflected by an almost doubling of measured MPVA among the men in GH (45 min/d) and SA (47 min/d) compared to only 28 min/d in the US. Women in GH (25 min/d), SA (21 min/d), JA (20 min/d) and SEY (20 min/d) accumulated significantly more MPVA than women in the US (14 min/d), yet this difference was not reflected by differences in BMI between SA, JA, SEY and US. Moderate PA constituted the bulk of the PA, with no study populations except SA men accumulating > 5 min/d of vigorous PA. Among the women, no sites accumulated >2 min/d of vigorous PA. Overweight/obese men were 22% less likely to engage in manual occupations. CONCLUSION: While there is some association for PA with obesity, this relationship is inconsistent across the epidemiologic transition and suggests that PA policy recommendations should be tailored for each environment.

Patterns of neurovascular compression in patients with classic trigeminal neuralgia: A high-resolution MRI-based study.

PURPOSE: To describe the anatomical characteristics and patterns of neurovascular compression in patients suffering classic trigeminal neuralgia (CTN), using high-resolution magnetic resonance imaging (MRI). MATERIALS AND METHODS: The analysis of the anatomy of the trigeminal nerve, brain stem and the vascular structures related to this nerve was made in 100 consecutive patients treated with a Gamma Knife radiosurgery for CTN between December 1999 and September 2004. MRI studies (T1, T1 enhanced and T2-SPIR) with axial, coronal and sagital simultaneous visualization were dynamically assessed using the software GammaPlan?. Three-dimensional reconstructions were also developed in some representative cases. RESULTS: In 93 patients (93%), there were one or several vascular structures in contact, either, with the trigeminal nerve, or close to its origin in the pons. The superior cerebellar artery was involved in 71 cases (76%). Other vessels identified were the antero-inferior cerebellar artery, the basilar artery, the vertebral artery, and some venous structures. Vascular compression was found anywhere along the trigeminal nerve. The mean distance between the nerve compression and the origin of the nerve in the brainstem was 3.76±2.9mm (range 0-9.8mm). In 39 patients (42%), the vascular compression was located proximally and in 42 (45%) the compression was located distally. Nerve dislocation or distortion by the vessel was observed in 30 cases (32%). CONCLUSIONS: The findings of this study are similar to those reported in surgical and autopsy series. This non-invasive MRI-based approach could be useful for diagnostic and therapeutic decisions in CTN, and it could help to understand its pathogenesis.