BACKGROUND:People living with HIV (PLWH) experience a higher cardiovascular disease (CVD) risk. Yet, traditional algorithms are often used to estimate CVD risk. We evaluated the performance of 4 ...commonly used algorithms.
SETTING:The Netherlands.
METHODS:We used data from 16,070 PLWH aged ≥18 years, who were in care between 2000 and 2016, had no pre-existing CVD, had initiated first combination antiretroviral therapy >1 year ago, and had available data on CD4 count, smoking status, cholesterol, and blood pressure. Predictive performance of 4 algorithms Data Collection on Adverse Effects of Anti-HIV Drugs Study (D:A:D); Systematic COronary Risk Evaluation adjusted for national data (SCORE-NL); Framingham CVD Risk Score (FRS); and American College of Cardiology and American Heart Association Pooled Cohort Equations (PCE) was evaluated using a Kaplan–Meier approach. Model discrimination was assessed using Harrellʼs C-statistic. Calibration was assessed using observed-versus-expected ratios, calibration plots, and Greenwood-Nam-DʼAgostino goodness-of-fit tests.
RESULTS:All algorithms showed acceptable discrimination (Harrellʼs C-statistic 0.73–0.79). On a population level, D:A:D, SCORE-NL, and PCE slightly underestimated, whereas FRS slightly overestimated CVD risk (observed-versus-expected ratios 1.35, 1.38, 1.14, and 0.92, respectively). D:A:D, FRS, and PCE best fitted our data but still yielded a statistically significant lack of fit (Greenwood-Nam-DʼAgostino χ ranged from 24.57 to 34.22, P < 0.05). Underestimation of CVD risk was particularly observed in low-predicted CVD risk groups.
CONCLUSIONS:All algorithms perform reasonably well in PLWH, with SCORE-NL performing poorest. Prediction algorithms are useful for clinical practice, but clinicians should be aware of their limitations (ie, lack of fit and slight underestimation of CVD risk in low-risk groups).
The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined ...mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains.
As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters.
The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
ObjectivesEarly testing for HIV and entry into care are crucial to optimise treatment outcomes of HIV-infected patients and to prevent spread of HIV. We examined risk factors for presentation with ...late or advanced disease in HIV-infected patients in the Netherlands.MethodsHIV-infected patients registered in care between January 1996 and June 2014 were selected from the ATHENA national observational HIV cohort. Risk factors for late presentation and advanced disease were analysed by multivariable logistic regression. Furthermore, geographical differences and time trends were examined.ResultsOf 20 965 patients, 53% presented with late-stage HIV infection, and 35% had advanced disease. Late presentation decreased from 62% (1996) to 42% (2013), while advanced disease decreased from 46% to 26%. Late presentation only declined significantly among men having sex with men (MSM; p <0.001), but not among heterosexual males (p=0.08) and females (p=0.73). Factors associated with late presentation were: heterosexual male (adjusted OR (aOR), 1.59; 95% CI 1.44 to 1.75 vs MSM), injecting drug use (2.00; CI 1.69 to 2.38), age ≥50 years (1.46; CI 1.33 to 1.60 vs 30–49 years), region of origin (South-East Asia 2.14; 1.80 to 2.54, sub-Saharan Africa 2.11; 1.88 to 2.36, Surinam 1.59; 1.37 to 1.84, Caribbean 1.31; 1.13 to 1.53, Latin America 1.23; 1.04 to 1.46 vs the Netherlands), and location of HIV diagnosis (hospital 3.27; 2.94 to 3.63, general practitioner 1.66; 1.50 to 1.83, antenatal screening 1.76; 1.38 to 2.34 vs sexually transmitted infection clinic). No association was found for socioeconomic status or level of urbanisation. Compared with Amsterdam, 2 regions had higher adjusted odds and 2 regions had lower odds of late presentation. Results were highly similar for advanced disease.ConclusionsAlthough the overall rate of late presentation is declining in the Netherlands, targeted programmes to reduce late HIV diagnoses remain needed for all risk groups, but should be prioritised for heterosexual males, migrant populations, people aged ≥50 years and certain regions in the Netherlands.
BACKGROUND:Whether continued, accelerated liver fibrosis progression occurs following acute hepatitis C virus infection (AHCVI) in HIV-positive MSM is unknown.
DESIGN AND METHODS:HIV-positive MSM ...from the AIDS Therapy Evaluation in the Netherlands and MSM Observational Study for Acute Infection with Hepatitis C-cohorts with primary AHCVI and at least one fibrosis-4 (FIB-4) measurement less than 2 years before and 1 year after estimated AHCVI were included. Mixed-effect linear models were used to evaluate (time-updated) determinants of FIB-4 levels over time. Determinants of transitioning to and from FIB-4 ≤ 1.45 and > 1.45 were examined using multistate Markov models.
RESULTS:Of 313 MSM, median FIB-4 measurements per individual was 12 (interquartile range = 8–18) and median follow-up following AHCVI was 3.5 years (interquartile range = 1.9–5.6). FIB-4 measurements averaged at 1.00 95% confidence interval (CI) = 0.95–1.05 before AHCVI, 1.31 (95% CI = 1.25–1.38) during the first year of AHCVI and 1.10 (95% CI = 1.05–1.15) more than 1 year after AHCVI. Mean FIB-4 more than 1 year after AHCVI was higher for chronically infected patients compared with those successfully treated (P = 0.007). Overall FIB-4 scores were significantly higher with older age, lower CD4 cell count, longer duration from HIV-diagnosis or AHCVI, and nonresponse to HCV-treatment. At the end of follow-up, 60 (19.2%) and eight MSM (2.6%) had FIB-4 between 1.45–3.25 and ≥ 3.25, respectively. Older age, lower CD4 cell count and detectable HIV-RNA were significantly associated with higher rates of progression to FIB-4 > 1.45, whereas older age, longer duration from HIV-diagnosis and nonresponse to HCV-treatment were significantly associated with lower rates of regression to FIB-4 ≤ 1.45.
CONCLUSION:In this population of HIV-positive MSM, FIB-4 scores were higher during the first year of AHCVI, but FIB-4 ≥ 3.25 was uncommon by the end of follow-up. Well controlled HIV-infection appears to attenuate FIB-4 progression.
Despite significant progress made in the overall cure rate, the prognosis for relapsed and refractory malignancies in children remains extremely poor. Hence, there is an urgent need for studies that ...enable the timely selection of appropriate agents for Phase I clinical studies. The Pediatric Oncology Experimental Therapeutics Investigators' Consortium (POETIC) is systematically evaluating libraries of known and novel compounds for activity against subsets of high-risk pediatric malignancies with defined molecular aberrations for future clinical development. In this report, we describe the in-vitro activity of a diverse panel of approved oncology drugs against MLL-rearranged pediatric leukemia cell lines. Agents in the Approved Oncology Drug Set II (National Cancer Institute/National Institutes of Health Developmental Therapeutics Program) were evaluated by in-vitro cytotoxicity assays in pediatric acute lymphoblastic leukemia and acute myeloid leukemia cell lines with MLL gene rearrangements. Validation studies were carried out with patient leukemia cells in culture. Comparative analysis for toxicity against nonmalignant cells was evaluated in normal bone marrow stromal cells and normal human lymphocytes. Results from this study show that 42 of the 89 agents tested have measurable cytotoxicity against leukemia cells, and among these, 12 were effective against all five MLL-rearranged cell lines (IC(50) half maximal inhibitory concentration < 1 μM). These 12 agents include cladribine, dactinomycin, daunorubicin, docetaxel, etoposide, gemcitabine, mitomycin C, mitoxantrone, teniposide, topotecan, triethylenemelamine, and vinblastine. We show that the Approved Oncology Drug Set II contains a number of agents with potent antileukemic activity in the tested cell lines. As approved drugs, these agents have been used in clinical settings for many years for other malignancies, thus their toxicity profile, pharmacokinetics, and other properties are readily available. Further evaluation of their use in future clinical trials for pediatric leukemia with MLL abnormalities should be considered.
This paper describes an educational application that combines handhelds (PDAs) and programmable Lego bricks in a classroom scenario that deals with the problem of letting a robot escape from a maze. ...It is specific to our setting that the problem can be solved both in the physical world by steering a Lego robot and in a simulated software environment on a PDA or on a PC. This approach enables the students to generate successful sets of rules in the simulation and to test these sets of rules later in physical mazes, or to create new types of mazes as challenges for known rule sets. In this paper we describe the technical setting for this scenario, different pedagogical scenarios and we will report an evaluation with a group of students in a school environment.
The astronomy domain provides rich opportunities for learning about natural phenomena. It can involve and motivate a variety of mathematical and physical knowledge and skills. However it is difficult ...to connect astronomic observations to modelling and calculation tools and to embed them into educational scenarios. It is particularly this challenge which is focused in this paper. Concretely, we build on an existing collaborative modelling framework (Cool Modes) and extend it with specific representations to support learning activities in astronomy. A first field test has been conducted with these extensions.
The CONNECT project proposes a pedagogical and technological approach that crosscuts the boundaries between schools and science museums and involves both students and teachers in extended episodes of ...playful learning. It develops tests and evaluates learning pathways to facilitate in situ learning that will be implemented in ambient, always available educational environments developed with emerging technology. This paper focuses on the first results from the project's implementation in Greece
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