Significant improvements in self-reported gastrointestinal tolerability, quality of life, patient satisfaction, and adherence with lopinavir/ritonavir tablet formulation compared with soft gel capsules

<p>Abstract</p> <p>Background</p> <p>The tablet formulation of ritonavir-boosted lopinavir (LPV/r; Kaletra^®) has many advantages over the soft gel capsule (SGC) formulation, including lower pill count, no refrigeration requirement, and no dietary restrictions. These advantages may help improve patient compliance and therefore increase adherence to treatment. However, there are limited data regarding patient preferences and only recently was the comparative efficacy and tolerability data of LPV/r SGC versus tablet formulation presented at an international conference. To address this deficit, we conducted a market research survey to assess potential tolerability benefits, patient satisfaction, changes in adherence, and formulation preference in patients switching from SGCs to the tablet formulation. Data from 332 patients who switched from LPV/r SGCs twice-daily (BID) to tablets BID and 41 patients who switched from LPV/r SGCs BID or once daily (QD) to tablets QD were analyzed.</p> <p>Results</p> <p>Switching from SGCs to a tablet formulation of LPV/r was associated with increased patient satisfaction, tolerability and self-reported adherence to treatment; gastrointestinal side effects were reduced. In addition, respondents indicated that they preferred the tablet formulation to the SGC.</p> <p>Conclusion</p> <p>The LPV/r tablet formulation provides HIV-infected patients with multiple benefits over the SGC in terms of tolerability and convenience. Additional assessments to further define the tolerability profile of the LPV/r tablet, including studies using once-daily dosing, are warranted.</p

A Test-Retest Reliability Generalization Meta-Analysis of Judgments Via the Policy-Capturing Technique

Policy capturing is a widely used technique, but the temporal stability of policy-capturing judgments has long been a cause for concern. This article emphasizes the importance of reporting reliability, and in particular test-retest reliability, estimates in policy-capturing studies. We found that only 164 of 955 policy-capturing studies (i.e., 17.17%) reported a test-retest reliability estimate. We then conducted a reliability generalization meta-analysis on policy-capturing studies that did report test-retest reliability estimates—and we obtained an average reliability estimate of .78. We additionally examined 16 potential methodological and substantive antecedents to test-retest reliability (equivalent to moderators in validity generalization studies). We found that test-retest reliability was robust to variation in 14 of the 16 factors examined but that reliability was higher in paper-and-pencil studies than in web-based studies and was higher for behavioral intention judgments than for other (e.g., attitudinal and perceptual) judgments. We provide an agenda for future research. Finally, we provide several best-practice recommendations for researchers (and journal reviewers) with regard to (a) reporting test-retest reliability, (b) designing policy-capturing studies for appropriate reportage, and (c) properly interpreting test-retest reliability in policy-capturing studies

The Givenness of the Human Learning Experience and Its Incompatibility with Information Analytics

The rise of learning analytics, the application of complex metrics developed to exploit the proliferation of ‘Big Data’ in educational work, raises important moral questions about the nature of what is measurable in education. Teachers, schools and nations are increasingly held to account based on metrics, exacerbating the tendency for fine-grained measurement of learning experiences. In this article, the origins of learning analytics ontology are explored, drawing upon core ideas in the philosophy of computing, such as the general definition of information and the information-theoretic account of knowledge. Drawing upon a reading of Descartes Meditatio II, which extends the phenomenology of Jean-Luc Marion into a pedagogy of intentionality, the article identifies a fundamental incompatibility between the subjective experience of learning and the information-theoretic account of knowledge. Human subjects experience and value their own information incommensurably with the ways in which computers measure and quantify information. The consequences of this finding for the design of online learning environments, and the necessary limitations of learning analytics and measurement are explored

4D-Var inversion of European NH3 emissions Using CrIS NH3 measurements and GEOS-Chem adjoint with bi-directional and uni-directional flux schemes

We conduct the first 4D-Var inversion of NH3 accounting for NH3 bi-directional flux, using CrIS satellite NH3 observations over Europe in 2016. We find posterior NH3 emissions peak more in springtime than prior emissions at continental to national scales, and annually they are generally smaller than the prior emissions over central Europe, but larger over most of the rest of Europe. Annual posterior anthropogenic NH3 emissions for 25 European Union members (EU25) are 25% higher than the prior emissions and very close (<2% difference) to other inventories. Our posterior annual anthropogenic emissions for EU25, the UK, the Netherlands, and Switzerland are generally 10%–20% smaller than when treating NH3 fluxes as uni-directional emissions, while the monthly regional difference can be up to 34% (Switzerland in July). Compared to monthly mean in-situ observations, our posterior NH3 emissions from both schemes generally improve the magnitude and seasonality of simulated surface NH3 and bulk NHx wet deposition throughout most of Europe, whereas evaluation against hourly measurements at a background site shows the bi-directional scheme better captures observed diurnal variability of surface NH3. This contrast highlights the need for accurately simulating diurnal variability of NH3 in assimilation of sun-synchronous observations and also the potential value of future geostationary satellite observations. Overall, our top-down ammonia emissions can help to examine the effectiveness of air pollution control policies to facilitate future air pollution management, as well as helping us understand the uncertainty in top-down NH3 emissions estimates associated with treatment of NH3 surface exchange

Efficacy and safety of etravirine (TMC125) in patients with highly resistant HIV-1: primary 24-week analysis

TMC125-C223 is an open-label, partially blinded, randomized clinical trial to evaluate the efficacy and safety of two dosages of etravirine (TMC125), a non-nucleoside reverse transcriptase inhibitor (NNRTI) with activity against wild-type and NNRTI-resistant HIV-1.A total of 199 patients were randomly assigned 2: 2: 1 to twice-daily etravirine 400 mg, 800 mg and control groups, respectively. The primary endpoint was a change in viral load from baseline at week 24 in the intention-to-treat population.Patients had HIV-1 with genotypic resistance to approved NNRTIs and at least three primary protease inhibitor (PI) mutations. Etravirine groups received an optimized background of at least two approved antiretroviral agents [nucleoside reverse transcriptase inhibitors (NRTI) and/or lopinavir/ritonavir and/or enfuvirtide]. Control patients received optimized regimens of at least three antiretroviral agents (NRTIs or PIs and/or enfuvirtide).The mean change from baseline in HIV-1 RNA at week 24 was -1.04, -1.18 and -0.19 log10 copies/ml for etravirine 400 mg twice a day, 800 mg twice a day and the control group, respectively (P < 0.05 for both etravirine groups versus control). Etravirine showed no dose-related effects on safety and tolerability. No consistent pattern of neuropsychiatric symptoms was observed. There were few hepatic adverse events, and rashes were predominantly early onset and mild to moderate in severity.Etravirine plus an optimized background significantly reduced HIV-1-RNA levels from baseline after 24 weeks in patients with substantial NNRTI and PI resistance, and demonstrated a favorable safety profile compared with control