The Brazilian private pharmaceutical market after the first ten years of the generics law

Objectives: To describe changes in the private market for selected originators, branded generics (\u27similares\u27), and generic products during the 10 years following passage of the Brazilian Generics Law. Methods: We analyzed longitudinal data collected by IQVIA(R) on quarterly sales by wholesalers to retail pharmacies in Brazil from 1998 through 2010, grouped by originators, branded generics, and generic products in three therapeutic classes (antibiotics, antidiabetics, and antihypertensives). Outcomes included market share (proportion of the total private market volume), sales volume per capita, prices and number of manufacturers by group. Results: In the private market share, generics became dominant in each therapeutic class but the speed of uptake varied. Originators consistently lost most market share while branded generics varied over time. By the end of the study period, generics were the most sold product type in all classes, followed by branded generics. The number of generic manufacturers increased in all classes, while branded generics increased just after the policy but then decreased slowly through the end of 2010. For approximately 50% of the antibiotics analyzed, branded generics and generics had lower prices than originators. For antidiabetics, branded generic and generic prices were quite similar during the period analyzed. Price trends for the various subclasses of antihypertensive exhibited very different patterns over time. Conclusion: Sales of branded generics and originators decreased substantially in the three therapeutic classes analysed following the introduction of the generics policy in Brazil, but the time to market dominance of generics varied by class

Equatorial Pacific productivity changes near the Eocene-Oligocene boundary

There is general agreement that productivity in high latitudes increased in the late Eocene and remained high in the early Oligocene. Evidence for both increased and decreased productivity across the Eocene-Oligocene transition (EOT) in the tropics has been presented, usually based on only one paleoproductivity proxy and often in sites with incomplete recovery of the EOT itself. A complete record of the Eocene-Oligocene transition was obtained at three drill sites in the eastern equatorial Pacific Ocean (ODP Site 1218 and IODP Sites U1333 and U1334). Four paleoproductivity proxies that have been examined at these sites, together with carbon and oxygen isotope measurements on early Oligocene planktonic foraminifera, give evidence of ecologic and oceanographic change across this climatically important boundary. Export productivity dropped sharply in the basal Oligocene (~33.7�Ma) and only recovered several hundred thousand years later; however, overall paleoproductivity in the early Oligocene never reached the average levels found in the late Eocene and in more modern times. Changes in the isotopic gradients between deep- and shallow-living planktonic foraminifera suggest a gradual shoaling of the thermocline through the early Oligocene that, on average, affected accumulation rates of barite, benthic foraminifera, and opal, as well as diatom abundance near 33.5�Ma. An interval with abundant large diatoms beginning at 33.3�Ma suggests an intermediate thermocline depth, which was followed by further shoaling, a dominance of smaller diatoms, and an increase in average primary productivity as estimated from accumulation rates of benthic foraminifera

Nucleosynthesis in ONeMg Novae: Models versus Observations to Constrain the Masses of ONeMg White Dwarfs and Their Envelopes

Nucleosynthesis in ONeMg novae has been investigated with the wide ranges of three parameters, i.e., the white dwarf mass, the envelope mass at ignition, and the initial composition. A quasi-analytic one-zone approach is used with an up-to-date nuclear reaction network. The nucleosynthesis results show correlation with the peak temperatures or the cooling timescales during outbursts. Among the combinations of white dwarf and envelope masses which give the same peak temperature, the explosion is more violent for a lower white dwarf mass owing to its smaller gravitational potential. Comparison of the nucleosynthesis results with observations implies that at least two-third of the white dwarf masses for the observed ONeMg novae are $\simeq 1.1 M_\odot$, which are significantly lower than estimated by previous hydrodynamic studies but consistent with the observations of V1974 Cyg. Moreover, the envelope masses derived from the comparison are $\gtrsim 10^{-4} M_\odot$, which are in good agreement with the ejecta masses estimated from observations but significantly higher than in previous hydrodynamic studies. With such a low mass white dwarf and a high mass envelope, the nova can produce interesting amounts of $\gamma$-ray emitters $^7$Be, $^{22}$Na, and $^{26}$Al. We suggest that V1974 Cyg has produced $^{22}$Na as high as the upper limit derived from the COMPTEL survey. In addition, a non-negligible part of the Galactic $^{26}$Al may originate from ONeMg novae, if not the major contributors. Both the future INTEGRAL survey for these $\gamma$-ray emitters and abundance estimates derived from ultraviolet, optical, and near infrared spectroscopies will impose a severe constraint on the current nova models.Comment: 21 pages, 23 figures, to appear in the Astrophysical Journal, Vol. 523, No.1, September 20, 1999; preprint with embedded images can be obtained from http://th.nao.ac.jp/~wanajo/journal/onenova.p

Primary care management for optimized antithrombotic treatment [PICANT]: study protocol for a cluster-randomized controlled trial

Background: Antithrombotic treatment is a continuous therapy that is often performed in general practice and requires careful safety management. The aim of this study is to investigate whether a best practice model that applies major elements of case management, including patient education, can improve antithrombotic management in primary health care in terms of reducing major thromboembolic and bleeding events. Methods: This 24-month cluster-randomized trial will be performed in 690 adult patients from 46 practices. The trial intervention will be a complex intervention involving general practitioners, health care assistants and patients with an indication for oral anticoagulation. To assess adherence to medication and symptoms in patients, as well as to detect complications early, health care assistants will be trained in case management and will use the Coagulation-Monitoring-List (Co-MoL) to regularly monitor patients. Patients will receive information (leaflets and a video), treatment monitoring via the Co-MoL and be motivated to perform self-management. Patients in the control group will continue to receive treatment-as-usual from their general practitioners. The primary endpoint is the combined endpoint of all thromboembolic events requiring hospitalization, and all major bleeding complications. Secondary endpoints are mortality, hospitalization, strokes, major bleeding and thromboembolic complications, severe treatment interactions, the number of adverse events, quality of anticoagulation, health-related quality of life and costs. Further secondary objectives will be investigated to explain the mechanism by which the intervention is effective: patients' assessment of chronic illness care, self-reported adherence to medication, general practitioners' and health care assistants' knowledge, patients' knowledge and satisfaction with shared decision making. Practice recruitment is expected to take place between July and December 2012. Recruitment of eligible patients will start in July 2012. Assessment will occur at three time points: baseline (T0), follow-up after 12 (T1) and after 24 months (T2). Discussion: The efficacy and effectiveness of individual elements of the intervention, such as antithrombotic interventions, self-management concepts in orally anticoagulated patients and the methodological tool, case-management, have already been extensively demonstrated. This project foresees the combination of several proven instruments, as a result of which we expect to profit from a reduction in the major complications associated with antithrombotic treatment

Ohta-Jasnow-Kawasaki Approximation for Nonconserved Coarsening under Shear

We analytically study coarsening dynamics in a system with nonconserved scalar order parameter, when a uniform time-independent shear flow is present. We use an anisotropic version of the Ohta-Jasnow-Kawasaki approximation to calculate the growth exponents in two and three dimensions: for d=3 the exponents we find are the same as expected on the basis of simple scaling arguments, that is 3/2 in the flow direction and 1/2 in all the other directions, while for d=2 we find an unusual behavior, in that the domains experience an unlimited narrowing for very large times and a nontrivial dynamical scaling appears. In addition, we consider the case where an oscillatory shear is applied to a two-dimensional system, finding in this case a standard t^1/2 growth, modulated by periodic oscillations. We support our two-dimensional results by means of numerical simulations and we propose to test our predictions by experiments on twisted nematic liquid crystals.Comment: 25 RevTeX pages, 7 EPS figures. To be published in Phys. Rev.

The continuum limit of the static-light meson spectrum

We investigate the continuum limit of the low lying static-light meson spectrum using Wilson twisted mass lattice QCD with N_f = 2 dynamical quark flavours. We consider three values of the lattice spacing a ~ 0.051 fm, 0.064 fm, 0.080 fm and various values of the pion mass in the range 280 MeV < m_PS < 640 MeV. We present results in the continuum limit for light cloud angular momentum j = 1/2, 3/2, 5/2 and for parity P = +, -. We extrapolate our results to physical quark masses, make predictions regarding the spectrum of B and B_s mesons and compare with available experimental results.Comment: 18 pages, 3 figure

The association of health literacy with adherence in older 2 adults, and its role in interventions: a systematic meta-review

Background: Low health literacy is a common problem among older adults. It is often suggested to be associated with poor adherence. This suggested association implies a need for effective adherence interventions in low health literate people. However, previous reviews show mixed results on the association between low health literacy and poor adherence. A systematic meta-review of systematic reviews was conducted to study the association between health literacy and adherence in adults above the age of 50. Evidence for the effectiveness of adherence interventions among adults in this older age group with low health literacy was also explored. Methods: Eight electronic databases (MEDLINE, ERIC, EMBASE, PsycINFO, CINAHL, DARE, the Cochrane Library, and Web of Knowledge) were searched using a variety of keywords regarding health literacy and adherence. Additionally, references of identified articles were checked. Systematic reviews were included if they assessed the association between health literacy and adherence or evaluated the effectiveness of interventions to improve adherence in adults with low health literacy. The AMSTAR tool was used to assess the quality of the included reviews. The selection procedure, data-extraction, and quality assessment were performed by two independent reviewers. Seventeen reviews were selected for inclusion. Results: Reviews varied widely in quality. Both reviews of high and low quality found only weak or mixed associations between health literacy and adherence among older adults. Reviews report on seven studies that assess the effectiveness of adherence interventions among low health literate older adults. The results suggest that some adherence interventions are effective for this group. The interventions described in the reviews focused mainly on education and on lowering the health literacy demands of adherence instructions. No conclusions could be drawn about which type of intervention could be most beneficial for this population. Conclusions: Evidence on the association between health literacy and adherence in older adults is relatively weak. Adherence interventions are potentially effective for the vulnerable population of older adults with low levels of health literacy, but the evidence on this topic is limited. Further research is needed on the association between health literacy and general health behavior, and on the effectiveness of interventions

International Veterinary Epilepsy Task Force recommendations for systematic sampling and processing of brains from epileptic dogs and cats

Traditionally, histological investigations of the epileptic brain are required to identify epileptogenic brain lesions, to evaluate the impact of seizure activity, to search for mechanisms of drug-resistance and to look for comorbidities. For many instances, however, neuropathological studies fail to add substantial data on patients with complete clinical work-up. This may be due to sparse training in epilepsy pathology and or due to lack of neuropathological guidelines for companion animals. The protocols introduced herein shall facilitate systematic sampling and processing of epileptic brains and therefore increase the efficacy, reliability and reproducibility of morphological studies in animals suffering from seizures. Brain dissection protocols of two neuropathological centres with research focus in epilepsy have been optimised with regards to their diagnostic yield and accuracy, their practicability and their feasibility concerning clinical research requirements. The recommended guidelines allow for easy, standardised and ubiquitous collection of brain regions, relevant for seizure generation. Tissues harvested the prescribed way will increase the diagnostic efficacy and provide reliable material for scientific investigations

Microbial methane cycling in sediments of Arctic thermokarst lagoons

Thermokarst lagoons represent the transition state from a freshwater lacustrine to a marine environment, and receive little attention regarding their role for greenhouse gas production and release in Arctic permafrost landscapes. We studied the fate of methane (CH4) in sediments of a thermokarst lagoon in comparison to two thermokarst lakes on the Bykovsky Peninsula in northeastern Siberia through the analysis of sediment CH4 concentrations and isotopic signature, methane-cycling microbial taxa, sediment geochemistry, lipid biomarkers, and network analysis. We assessed how differences in geochemistry between thermokarst lakes and thermokarst lagoons, caused by the infiltration of sulfate-rich marine water, altered the microbial methane-cycling community. Anaerobic sulfate-reducing ANME-2a/2b methanotrophs dominated the sulfate-rich sediments of the lagoon despite its known seasonal alternation between brackish and freshwater inflow and low sulfate concentrations compared to the usual marine ANME habitat. Non-competitive methylotrophic methanogens dominated the methanogenic community of the lakes and the lagoon, independent of differences in porewater chemistry and depth. This potentially contributed to the high CH4 concentrations observed in all sulfate-poor sediments. CH4 concentrations in the freshwater-influenced sediments averaged 1.34 ± 0.98 μmol g−1, with highly depleted δ13C-CH4 values ranging from −89‰ to −70‰. In contrast, the sulfate-affected upper 300 cm of the lagoon exhibited low average CH4 concentrations of 0.011 ± 0.005 μmol g−1 with comparatively enriched δ13C-CH4 values of −54‰ to −37‰ pointing to substantial methane oxidation. Our study shows that lagoon formation specifically supports methane oxidizers and methane oxidation through changes in pore water chemistry, especially sulfate, while methanogens are similar to lake conditions

Phenotypic redshifts with self-organizing maps: A novel method to characterize redshift distributions of source galaxies for weak lensing

Wide-field imaging surveys such as the Dark Energy Survey (DES) rely on coarse measurements of spectral energy distributions in a few filters to estimate the redshift distribution of source galaxies. In this regime, sample variance, shot noise, and selection effects limit the attainable accuracy of redshift calibration and thus of cosmological constraints. We present a new method to combine wide-field, few-filter measurements with catalogs from deep fields with additional filters and sufficiently low photometric noise to break degeneracies in photometric redshifts. The multi-band deep field is used as an intermediary between wide-field observations and accurate redshifts, greatly reducing sample variance, shot noise, and selection effects. Our implementation of the method uses self-organizing maps to group galaxies into phenotypes based on their observed fluxes, and is tested using a mock DES catalog created from N-body simulations. It yields a typical uncertainty on the mean redshift in each of five tomographic bins for an idealized simulation of the DES Year 3 weak-lensing tomographic analysis of $\sigma_{\Delta z} = 0.007$, which is a 60% improvement compared to the Year 1 analysis. Although the implementation of the method is tailored to DES, its formalism can be applied to other large photometric surveys with a similar observing strategy.Comment: 24 pages, 11 figures; matches version accepted to MNRA