121 research outputs found
Adherence to prescribed antiretroviral therapy in human immunodeficiency virus infected children in the PENTA 5 trial
No full textBackground. Most studies of adherence to highly active antiretroviral therapy in children have been retrospective or cross-sectional. Factors relating to the caregiver, the child and the medication are all considered to be important for good adherence.
Methods. Adherence with taking prescribed medication was assessed by questionnaires completed at 4, 12, 24 and 48 weeks by caregivers of previously untreated HIV-infected children participating in the PENTA 5 trial, which was designed to evaluate different dual nucleoside reverse transcriptase inhibitor therapy combinations with and without the protease inhibitor nelfinavir. The effects of several factors on adherence and the effect of adherence on virologic suppression were assessed by multivariate logistic regression.
Results. Caregivers returned 266 questionnaires including at least 1 for 108 (84%) children in the trial. Nelfinavir was reported to be the most difficult drug to take (38% of questionnaires), but the difficulty decreased over time, P = 0.02. Comments on difficulties in taking and remembering drugs related to fear of disclosure and to unpleasant characteristics of the drugs. Full adherence was reported in 74% of questionnaires, did not change over time and was reported more frequently in children older than 10 years and those with symptomatic HIV disease. More children reporting full adherence achieved HIV RNA <400 copies/ml (e.g. at 48 weeks 79% vs. 50% reporting some nonadherence; overall P = 0.01).
Conclusion. Good adherence with taking prescribed medication was associated with virologic response. Social factors were important in explaining nonadherence
Pharmacokinetics of pediatric lopinavir/ritonavir tablets in children when administered twice daily according to FDA weight bands
No full textContains fulltext :
136012.pdf (Publisher’s version ) (Closed access)BACKGROUND: Lopinavir/ritonavir (LPV/r) pediatric tablets (100/25 mg) are approved by the United States Food and Drug Administration (FDA) and European Medicines Agency (EMA) as part of combination antiretroviral therapy. Dosing is based on body weight bands or body surface area under FDA approval and only body surface area by the EMA. This can lead to a different recommended dose. In addition, weight band-based dosing has not been formally studied in the target population. We evaluated the pharmacokinetics (PK) of LPV/r in children, administered twice daily according to the FDA weight bands, using pediatric tablets. METHODS: Fifty-three HIV-infected children were included in the PK substudy of the Paediatric European Network for the Treatment of AIDS 18 trial (KONCERT). In this study, children were randomized to receive LPV/r twice or once daily, according to FDA weight bands. A PK assessment was performed in 17, 16 and 20 children in the 15-25 kg, >/=25-35 kg and >35 kg weight band, respectively, while children took the tablets twice daily. Rich sampling was performed, and PK parameters were calculated by noncompartmental analysis. Given the high percentage of Asian children, it was also tested whether there was a difference in PK parameters between Asian and non-Asian children. RESULTS: For the total group, LPV geometric mean AUC0-12, Cmax and C12 were 106.9 h x mg/L, 12.0 mg/L and 4.9 mg/L, respectively. There were no significant differences in LPV PK parameters between the weight bands. In addition, weight was not found to be associated with variability in Cmax, C12 or AUC0-12 for the LPV PK parameters. CONCLUSIONS: FDA weight band-based dosing recommendations provide adequate exposure to LPV when using LPV/r pediatric tablets
Tailor-made consumer protection: personalisation’s impact on the granularity of consumer information
No full textThis is the author accepted manuscript. The final version is available from Edward Elgar Publishing via the link in this recordThis chapter illustrates how the use of the legal design principles and the benefits of
modern technology could guide EU policymakers in drafting more effective consumer protection
measures, specifically information provisions and information rules. As modern technology enables
personalisation of online information, the paper explores the option for this to lead to the rejection
of the one-size-fits-all approach embodied by the application of the average consumer benchmark
in assessing whether the information was transparent to consumers. The author proposes to
gradually oblige online traders to provide more granular, personalised information to consumers
Determination of Gamma-ee of the Upsilon(1S) and Upsilon(2S) Resonances, and Measurement of R At W = 9.39 GeV.
No full textUsing the Crystal Ball detector operating at the DORIS II storage ring we have measured the leptonic partial widths Fee of the Y(1S) and Y(2S) resonances. We find Gamma-ee(Y(1S)) = 1.34+-0.03+-0.06 keV andGamma-ee(Y(2S)) = 0.56+-0.04+-0.02 keV.The effect on Gamma-ee of applying different prescriptions for radiative corrections is discussed. W e also measure R, the ratio of non-resonant hadronic cross section to the Born cross section of mu pair production, at c.m. energy W = 9 . 3 9 G e V to beR=3.48+-0.04+-0.16
Relationship Among a Supernova, a Transition of Polarity of the Geomagnetic Field and the Pliocene-Pleistocene Boundary
No full textAfter the Middle Miocene, two important climatic changes took place, consisting mainly of cooling in both hemispheres. One occurred between 7.0 and 5.4 Ma and another at the end of the Pliocene, which marked the beginning of the Pleistocene in approximately 2.58 Ma. The proposal of thispresentation is to analyze diverse forcings of these climatic changes, such as the influence of the joint occurrence of reversions of the geomagnetic field andexplosions of a supernova. These events occurred coincidentally with thecooling of Earth. Also, biological changes in those time intervals are analyzed,especially the evolution of the Hominins since the oldest hominin fossils. Thecharacteristics of the Galactic Cosmic Rays, its influence on the climate and its potential mutogenetic effect were taken into account.Briefly, according to our analysis, it seems to be evident that together withother factors, the joint occurrence of the explosion of a supernova at less than100 pc from the Earth and the weakening and/or reversion of the GeomagneticField was an important factor that promoted these two climatic and ecosystemchanges.Fil: Compagnucci, Rosa Hilda. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Orgeira, Maria Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires; ArgentinaFil: Sinito, Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cappellotto, Luiggina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires; ArgentinaFil: Plastani, María Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; Argentin
Plasma drug concentrations and virologic evaluations after stopping treatment with nonnucleoside reverse-transcriptase inhibitors in HIV type 1-infected children
No full textBACKGROUND: The optimum strategy for stopping treatment with drugs that have different half-lives in a combination regimen to minimize the risk of selecting drug-resistant viruses remains unknown. We evaluated drug concentrations in plasma, human immunodeficiency virus (HIV) load, and development of drug resistance after a planned treatment interruption of a nonnucleoside reverse-transcriptase inhibitor (NNRTI)-containing regimen in HIV type 1-infected children. METHODS: Children with viral loads or =30% (for children aged 2-6 years) or CD4 cell percentages > or =25% and CD4 cell counts > or =500 cells/microL (for children aged 7-15 years) were randomized to either a planned treatment interruption or to continuous therapy. In the planned treatment interruption arm, either (1) treatment with nevirapine or efavirenz was stopped, and treatment with the remaining drugs was continued for 7-14 days, or (2) nevirapine or efavirenz were replaced by a protease inhibitor, and all drugs were stopped after 7-14 days. Sampling for determination of plasma drug concentrations, measurement of viral load, and drug resistance testing was scheduled at day 0, day 7 (drug concentrations only), day 14, and day 28 after interruption of treatment with an NNRTI. RESULTS: Treatment with an NNRTI was interrupted for 35 children (20 were receiving nevirapine, and 15 were receiving efavirenz). Median time from NNRTI cessation to stopping all drugs was 9 days (range, 6-15 days) for nevirapine and 14 days (range, 6-18 days) for efavirenz. At 7 days, 1 (5%) of 19 and 4 (50%) of 8 children had detectable nevirapine and efavirenz concentrations, respectively; efavirenz remained detectable in 3 (25%) of 12 children at 14 days. At 14 days, viral load was > or =50 copies/mL in 6 of 16 children interrupting treatment with nevirapine (range, 52-7000 copies/mL) and in 2 of 12 children interrupting treatment with efavirenz (range, 120-1600 copies/mL). No new NNRTI mutations were observed. CONCLUSIONS: In children with virological suppression who experienced interruption of treatment with an NNRTI, staggered or replacement stopping strategies for a median of 9 days for nevirapine and 14 days for efavirenz were not associated with the selection of NNRTI resistance mutations
Stratigraphy and rock magnetism in a profile at arroyo Tapalqué, Quaternary of Buenos Aires province: Palaeoenvironmental and palaeoclimatic implications
No full textIn the right bank of the Arroyo Tapalqué (Salto de Piedra, Olavarría, Buenos Aires province) is a section through fluvial sediments of the Luján Formation (upper and lower members) and aeolian deposits of La Postrera Formation. A geological and geophysical study was carried out to determination the magnetic parameters of the sediments of both formations, in order to evaluate the environmental and climatic conditions at the time of deposition. Levels with high concentrations of ferromagnetic minerals are thought to be related to an increase in capacity of river transport probably due to higher rainfall. By contrast, a particular magnetic behaviour was detected in levels closely associated with pedogenetic processes (Suelo Puesto Callejón Viejo, SPCV, Suelo Puesto Berrondo, SPB and present soils). This behaviour is attributed to the partial dissolution of the ferromagnetic fraction (magnetic/titanomagnetite) and to possible formation of a high c oercitivity magnetic fraction (hematite?) as an associated process. These results are similar to those obtained for paleosols from the Buenos Aires Formation, probably because of parental material common to both. On the basis of present field and laboratory observations, together with previously available information, a detailed correlation is proposed between features observed in this section and palaeoclimatic fluctuations identified for Pleistocene/Holocene.Fil:Orgeira, M.J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Walther, A.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Tófalo, R. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Vasquez, C.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Lippai, H. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Compagnucci, R. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Measurement of the direct photon spectrum from Υ(1S) decays
No full textUsing the Crystal Ball detector at the e+e- storage ring DORIS II, we have measured the energy spectrum of direct photons from Υ(1S) decays. According to QCD, these photons result from the decays of the Υ(1S) resonance into one photon and two gluons, Υ(1S) -> gamma g g -> gamma + hadrons. The shape of our spectrum does not agree with that calculated in lowest order QCD, but can be described well by a prediction incorporating gluon self-interaction. Using this fit, the ratio R-gamma = Gamma(Y -> gamma g g) / Gamma(Y -> ggg) is determined to be (2.7+-0.2+-0.4)%. From this ratio we deduce the strong coupling constant in the MS scheme at Q2 = 2.2 GeV^2 and find alpha-s = 0.25+-0.02+-0.04
Revision of the CNO cycle: Rate of O17 destruction in stars
No full textThe CNO cycle powers core H burning, in stars with M>1.2M⊙, and shell H burning, during the advanced evolutionary phases. Therefore, the uncertainties affecting the reaction rates of proton captures on C, N, and O isotopes limit our understanding of stellar evolution and nucleosynthesis. We aim to develop a general and self-consistent tool for the calculation of nuclear reaction rates and their uncertainties, starting from available experimental data. As a longer term plan, we intend to use this tool to revise the proton-capture reactions of the CNO cycle for which new experimental data are or will be available in the next future. The general procedure consists of R-matrix cross section calculations based on available measurements of the relevant nuclear parameters (energies, widths, strengths of known resonances, interference patterns, etc.), coupled to a Monte Carlo procedure to evaluate the global reaction rate error. A first application of this method to
17
O
(p,γ)
18
F
and
17
O
(p,α)
14
N
, the reactions that determine the
17
O
destruction in stellar interiors where the CNO cycle is active, is presented. These two reactions also allow us to test the multichannel and multilevel capabilities of the R-matrix method. In the temperature range of hydrostatic H burning (T<100 MK), we confirm that the median rates are up to a factor of 2 higher than those suggested in reaction rate libraries commonly used in stellar model calculations. In this temperature range, the 17 O destruction mainly proceeds through the 17 O (p,α) 14 N channel, whose rate is known within ±20% (95% C.L.). Based on current stellar models of red giant stars, we show that this uncertainty produces a 10% variation on the predicted 16O / 17 O abundance ratio. Other uncertainties, such as those affecting the 17 O
production rate, i.e., the 16O (p,γ) 17 F reaction, have a stronger impact on this theoretical prediction, a fact that motivates further experimental investigations of the 17 O production channel
Association of Premature Ventricular Contraction Burden on Serial Holter Monitoring with Arrhythmic Risk in Patients with Arrhythmogenic Right Ventricular Cardiomyopathy
No full textImportance: A high burden of premature ventricular contractions (PVCs) at disease diagnosis has been associated with an overall higher risk of ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy (ARVC). Data regarding dynamic modification of PVC burden at follow-up with Holter monitoring and its impact on arrhythmic risk in ARVC are scarce. Objective: To describe changes in the PVC burden and to assess whether serial Holter monitoring is dynamically associated with sustained ventricular arrhythmias during follow-up in patients with ARVC. Design, Settings, and Participants: In this cohort study, patients with a definite ARVC diagnosis, available Holter monitoring results at disease diagnosis, and at least 2 additional results of Holter monitoring during follow-up were enrolled from 6 ARVC registries in North America and Europe. Data were collected from June 1 to September 15, 2021. Main Outcomes and Measures: The association between prespecified variables retrieved at each Holter monitoring follow-up (ie, overall PVC burden; presence of sudden PVC spikes, defined as absolute increase in PVC burden ≥5000 per 24 hours or a relative ≥75% increase, with an absolute increase of ≥1000 PVCs; presence of nonsustained ventricular tachycardia [NSVT]; and use of β-blockers and class III antiarrhythmic drugs) and sustained ventricular arrhythmias occurring within 12 months after that Holter examination was assessed using a mixed logistical model. Results: In 169 enrolled patients with ARVC (mean [SD] age, 36.3 [15.0] years; 95 men [56.2%]), a total of 723 Holter examinations (median, 4 [IQR, 4-5] per patient) were performed during a median follow-up of 54 (IQR, 42-63) months and detected 75 PVC spikes and 67 sustained ventricular arrhythmias. The PVC burden decreased significantly from the first to the second Holter examination (mean, 2906 [95% CI, 1581-4231] PVCs per 24 hours; P <.001). A model including 24-hour PVC burden (odds ratio [OR] 1.50 [95% CI, 1.10-2.03]; P =.01), PVC spikes (OR, 6.20 [95 CI, 2.74-13.99]; P <.001), and NSVT (OR, 2.29 [95% CI, 1.10-4.51]; P =.03) at each follow-up Holter examination was associated with sustained ventricular arrhythmia occurrence in the following 12 months. Conclusions and Relevance: These findings suggest that in patients with ARVC, changes in parameters derived from each Holter examination performed during follow-up are associated with the risk of sustained ventricular arrhythmias within 12 months of disease diagnosis
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