Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

A História da Alimentação: balizas historiográficas

Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema

\u3csup\u3e13\u3c/sup\u3eC and \u3csup\u3e15\u3c/sup\u3eN Solid-State NMR of Partially Methyl Substituted Polyazines

The partially methylated polyazine series, which varies the number of methyl groups along the polyazine backbone, has been prepared. The number and substitution pattern of methyl groups were altered via a condensation reaction between an α,β-dicarbonyl and an α,β-dihydrazone using glyoxal, pyruvic aldehyde, 2,3-butanedione, glyoxal dihydrazone, pyruvic aldehyde dihydrazone, and 2,3-butanedione dihydrazone. All combinations of the above reagents were used, leading to nine different polymers. The polymers prepared with glyoxal dihydrazone exhibit hydroxy-bearing defects like those in the unsubstituted polyazine. In contrast, the polymers prepared with 2,3-butanedione dihydrazone were essentially defect-free, like the permethyl and higher alkyl polyazines. However, the polymers prepared with pyruvic aldehyde dihydrazone failed to follow a simple trend. © 1991, American Chemical Society. All rights reserved

Structure of Glyoxal Dihydrazone and Synthesis, Characterization, and Iodine Doping of Unsubstituted Polyazine

The unsubstituted polyazine, -[N=CH-CH=N]X-, has been synthesized from glyoxal dihydrazone and glyoxal. An X-ray crystal structure was done on the monomer glyoxal dihydrazone; it crystallized in space group P21/a with cell constants a = 7.744 (4) Å, b = 4.113 (1) Å, c = 8.063 (4) Å, and β = 115.66 (3)° and Z = 2; intensity data were collected in the range 3.5 ≤ 2θ ≤ 60°. Refinement to convergence of the 683 independent reflections, I \u3e 3σ(I), resulted in final anisotropic R = 0.056 and Rw = 0.059. The monomer is planar with a carbon-nitrogen double bond (1.278 Å) in the E conformation and a short carbon-carbon single bond (1.433 Å) in the anti conformation, similar to the methyl-substituted analogue, 2,3-butanedione dihydrazone. The polymer also appears to adopt the anti-E conformation and so is directly comparable to transpolyacetylene. Both IR and solid-state NMR analyses show the presence of hydroxy-bearing defect sites; the azines are formed by an addition-elimination condensation, and the defects arise from sites where addition occurs but the subsequent elimination does not. Polyazine can be doped with iodine to give powders with room-temperature, pressed-pellet conductivities only as high as 1 X 10-6 Ω-1 cm-1 because of the sp3 defects found along the polymer chain. The IR spectra of the doped materials indicate that the charge carrier is a bipolaron having a nitrogen-nitrogen or carbon-carbon double bond. © 1990, American Chemical Society. All rights reserved

Direct Evidence of a Bipolaron Charge Carrier in Conducting Polyazines from \u3csup\u3e13\u3c/sup\u3eC and \u3csup\u3e15\u3c/sup\u3eN Solid-State NMR Spectroscopy: Detection of a Nitrenium Cation by Natural Abundance \u3csup\u3e15\u3c/sup\u3eN Solid-State NMR Spectroscopy

Natural abundance 13C and l5N solid-state NMR experiments were performed on undoped and doped samples of polyazine, (−N=C(R)-C(R)=N−)x. The topology of the polymer requires that doping-induced charge carriers must be either polarons (radical cations) or bipolarons (dications). Magnetic susceptibility measurements shows that the iodine-doped polymers are diamagnetic, so the charge carriers must be bipolarons. The specific bipolaron charge carrier in polyazines has been identified; the nitrogens bear the charge primarily in the form of a nitrenium cation. This is the first report of a nitrenium cation detected by 15N solid-state NMR spectroscopy. Independent of the substitution of the polyazine, R = H or CH3, the same charge carrier is present. © 1991, American Chemical Society. All rights reserved

Microbial Community Functional Change during Vertebrate Carrion Decomposition

Microorganisms play a critical role in the decomposition of organic matter, which contributes to energy and nutrient transformation in every ecosystem. Yet, little is known about the functional activity of epinecrotic microbial communities associated with carrion. The objective of this study was to provide a description of the carrion associated microbial community functional activity using differential carbon source use throughout decomposition over seasons, between years and when microbial communities were isolated from eukaryotic colonizers (e.g., necrophagous insects). Additionally, microbial communities were identified at the phyletic level using high throughput sequencing during a single study. We hypothesized that carrion microbial community functional profiles would change over the duration of decomposition, and that this change would depend on season, year and presence of necrophagous insect colonization. Biolog EcoPlates™ were used to measure the variation in epinecrotic microbial community function by the differential use of 29 carbon sources throughout vertebrate carrion decomposition. Pyrosequencing was used to describe the bacterial community composition in one experiment to identify key phyla associated with community functional changes. Overall, microbial functional activity increased throughout decomposition in spring, summer and winter while it decreased in autumn. Additionally, microbial functional activity was higher in 2011 when necrophagous arthropod colonizer effects were tested. There were inconsistent trends in the microbial function of communities isolated from remains colonized by necrophagous insects between 2010 and 2011, suggesting a greater need for a mechanistic understanding of the process. These data indicate that functional analyses can be implemented in carrion studies and will be important in understanding the influence of microbial communities on an essential ecosystem process, carrion decomposition

Mortality of treated HIV-1 positive individuals according to viral subtype in Europe and Canada: collaborative cohort analysis

Objectives: To estimate prognosis by viral subtype in HIV-1-infected individuals from start of antiretroviral therapy (ART) and after viral failure. Design: Collaborative analysis of data from eight European and three Canadian cohorts. Methods: Adults (N>20 000) who started triple ART between 1996 and 2012 and had data on viral subtype were followed for mortality. We estimated crude and adjusted (for age, sex, regimen, CD4þ cell count, and AIDS at baseline, period of starting ART, stratified by cohort, region of origin and risk group) mortality hazard ratios (MHR) by subtype. We estimated MHR subsequent to viral failure defined as two HIV-RNA measurements greater than 500 copies/ml after achieving viral suppression. Results: The most prevalent subtypes were B (15 419; 74%), C (2091; 10%), CRF02AG (1057; 5%), A (873; 4%), CRF01AE (506; 2.4%), G (359; 1.7%), and D (232; 1.1%). Subtypes were strongly patterned by region of origin and risk group. During 104 649 person-years of observation, 1172/20 784 patients died. Compared with subtype B, mortality was higher for subtype A, but similar for all other subtypes. MHR for A versus B were 1.13 (95% confidence interval 0.85,1.50) when stratified by cohort, increased to 1.78 (1.27,2.51) on stratification by region and risk, and attenuated to 1.59 (1.14,2.23) on adjustment for covariates. MHR for A versus B was 2.65 (1.64,4.28) and 0.95 (0.57,1.57) for patients who started ART with CD4þ cell count below, or more than, 100 cells/ml, respectively. There was no difference in mortality between subtypes A, B and C after viral failure. Conclusion: Patients with subtype A had worse prognosis, an observation which may be confounded by socio-demographic factors

Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes

Background Treatment strategies for patients in whom HIV replication is not suppressed after exposure to several drug classes remain unclear. We aimed to assess the inter-relations between viral load, CD4-cell count, and clinical outcome in patients who had experienced three-class virological failure. Methods We undertook collaborative joint analysis of 13 HIV cohorts from Europe, North America, and Australia, involving patients who had had three-class virological failure (viral load >1000 copies per mL for >4 months). Regression analyses were used to quantify the associations between CD4-cell-count slope, HIV-1 RNA concentration, treatment information, and demographic characteristics. Predictors of death were analysed by Cox's proportional-hazards models. Findings 2488 patients were included. 2118 (85%) had started antiretroviral therapy with single or dual therapy. During 5015 person-years of follow-up, 276 patients died (mortality rate 5.5 per 100 person-years; 3-year mortality risk 15.3% (95% Cl 13.5-17.3). Risk of death was strongly influenced by the latest CD4-cell count with a relative hazard of 15.8 (95% CI 9.28-27.0) for counts below 50 cells per muL versus above 200 cells per muL. The latest viral load did not independently predict death. For any given viral load, patients on treatment had more favourable CD4-cell-count slopes than those off treatment. For patients on treatment and with stable viral load, CD4-cell counts tended to be increasing at times when the current viral load was below 10 000 copies per mL or 1.5 log(10) copies per mL below off-treatment values. Interpretation In patients for whom viral-load suppression to below the level of detection is not possible, achievement and maintenance of a CD4-cell count above 200 per muL becomes the primary aim. Treatment regimens that maintain the viral load below 10 000 copies per mL or at least provide 1.5 log(10) copies per mL suppression below the off-treatment value do not seem to be associated with appreciable CD4-cell-count decline