Actual treatment of attention deficit hyperactivity disorder (ADHD)

El tratamiento del trastorno por défi cit de atención e hiperactividad (TDAH) incluye intervenciones farmacológicas, psicosociales y educativas, y en él se aconseja un diseño personalizado teniendo en cuenta las características del paciente, el tipo de trastorno y la comorbilidad que lo acompaña. Los fármacos de primera línea son el psicoestimulante metilfenidato (MTF) y atomoxetina (ATX), un simpaticomimético de acción central no estimulante. Ambos reducen las manifestaciones clínicas de inquietud, inatención e impulsividad, mejorando la calidad de las relaciones sociales y el rendimiento académico. Metilfenidato bloquea el transportador presináptico de dopamina (DA) y noradrenalina (NA), aumentando la concentración de estos neurotransmisores en el espacio presináptico neuronal. Se presenta en formas de liberación inmediata (LI) (Rubifen® y Medicebran® en preparados de acción prolongada con tecnología OROS® [osmotic controlled-release oral delivery system], Concerta® y Metilfenidato Sandoz®) y en pellets (Medikinet®), que permiten seleccionar adecuadamente la dosis y la pauta posológica. Las formas de LI pueden inducir efecto rebote al provocar un pico plasmático elevado que decae en poco tiempo. Atomoxetina (Strattera®) es un inhibidor muy selectivo y potente del transportador presináptico de NA; aumenta los niveles de NA y DA en la corteza prefrontal, pero no en las regiones corticales relacionadas con el desarrollo de tics o riesgo de abusos de sustancias. Puede ser la alternativa a MTF cuando éste pierde efi cacia o está contraindicado. La efectividad de ambos fármacos debe considerarse a partir de las 2-4 semanas. Sus reacciones adversas son numerosas y con frecuencia causan malestar, lo que difi culta la adherencia. Por ello es necesario el seguimiento de estos pacientes, y el farmacéutico puede ejercer un papel destacado para mejorar el cumplimiento y los efectos de la farmacoterapiaTreatment of attention defi cit hyperactivity disorder (ADHD) includes pharmacological, psychosocial and educational interventions. A custom designed treatment taking into account patient characteristics, type of disorder and comorbidity must be advisable. First election drugs are the psychostimulant methylphenidate (MTF) and the sympathomimetic not stimulant atomoxetine (ATX). These drugs reduce the clinical manifestations of restlessness, inattention and impulsivity, improving the quality of social relationships and academic performance. MTF blocks the presynaptic dopamine (DA) and norepinephrine (NA) transporters increasing the concentration of these neurotransmitters in the presynaptic neuron. Both of them are available in the pharmaceutical forms of immediate release (IR) (Rubifen ® and Medicebran®, prolonged acting preparations with OROS® [osmotic controlled-release oral delivery system] technology, Con certa® and Metilfenidato Sandoz®) and pellets (Medikinet®), allowing a proper selection of dosage pattern. IR pharmaceutical forms can induce rebounding effect by causing high plasma peak that decays quickly. ATX is a highly selective and a potent inhibitor of presynaptic NA transporter, increasing levels of NA and DA in the prefrontal cortex, but not in cortical regions related to the development of tics or risk of substance abuse. It can be an alternative to MTF when this loses effectiveness or is contraindicated. The effectiveness of both drugs must be considered after 2 to 4 weeks of treatment. Their side effects are numerous and often cause discomfort making diffi cult adherence. Therefore it is necessary to monitor these patients playing pharmacist a leading role in improving the performance and the effects of pharmacotherap

Descripción de la hembra de Pintomyia (Pifanomyia) deorsa (Diptera, Psychodidae, Phlebotominae)

Pintomyia (Pifanomyia) deorsa (Pérez, Ogusuku, Monje & Young, 1991) was described on the basis of a single male; the female is being described here from specimens collected in Ollantaytambo, Cusco, Peru. Diagnoses for the Pintomyia genus, Pifanomyia subgenus, Verrucarum series and both sexes of Pi. deorsa are presented, as well as an identification key to distinguish the females of the Verrucarum series.Pintomyia (Pifanomyia) deorsa (Pérez, Ogusuku, Monje & Young, 1991) fue descrita en base a un solo espécimen macho; la hembra es descrita aquí a partir de especímenes colectados en Ollantaytambo, Cusco, Perú. El diagnóstico para en género Pintomyia, el subgénero Pifanomyia, la série Verrucarum y ambos sexos de Pi. deorsa son presentados, así como claves para la identificación y separación de las hembras de la serie Verrucarum

Branch xylem density variations across Amazonia

International audienceMeasurements of branch xylem density, Dx, were made for 1466 trees representing 503 species, sampled from 80 sites across the Amazon basin. Measured values ranged from 240 kg m?3 for a Brosimum parinarioides from Tapajos in West Pará, Brazil to 1130 kg m?3 for an Aiouea sp. from Caxiuana, Central Pará, Brazil. Analysis of variance showed significant differences in average Dx across the sample plots as well as significant differences between families, genera and species. A partitioning of the total variance in the dataset showed that geographic location and plot accounted for 33% of the variation with species identity accounting for an additional 27%; the remaining "residual" 40% of the variance accounted for by tree to tree (within species) variation. Variations in plot means, were, however, hardly accountable at all by differences in species composition. Rather, it would seem that variations of xylem density at plot level must be explained by the effects of soils and/or climate. This conclusion is supported by the observation that the xylem density of the more widely distributed species varied systematically from plot to plot. Thus, as well as having a genetic component branch xylem density is a plastic trait that, for any given species, varies according to where the tree is growing and in a predictable manner. Exceptions to this general rule may be some pioneers belonging to Pourouma and Miconia and some species within the genera Brosimum, Rinorea and Trichillia which seem to be more constrained in terms of this plasticity than most species sampled as part of this study

Large-scale patterns of turnover and basal area change in Andean forests

General patterns of forest dynamics and productivity in the Andes Mountains are poorly characterized. Here we present the first large-scale study of Andean forest dynamics using a set of 63 permanent forest plots assembled over the past two decades. In the North-Central Andes tree turnover (mortality and recruitment) and tree growth declined with increasing elevation and decreasing temperature. In addition, basal area increased in Lower Montane Moist Forests but did not change in Higher Montane Humid Forests. However, at higher elevations the lack of net basal area change and excess of mortality over recruitment suggests negative environmental impacts. In North-Western Argentina, forest dynamics appear to be influenced by land use history in addition to environmental variation. Taken together, our results indicate that combinations of abiotic and biotic factors that vary across elevation gradients are important determinants of tree turnover and productivity in the Andes. More extensive and longer-term monitoring and analyses of forest dynamics in permanent plots will be necessary to understand how demographic processes and woody biomass are responding to changing environmental conditions along elevation gradients through this century

Low exposure long-baseline neutrino oscillation sensitivity of the DUNE experiment

The Deep Underground Neutrino Experiment (DUNE) will produce world-leading neutrino oscillation measurements over the lifetime of the experiment. In this work, we explore DUNE's sensitivity to observe charge-parity violation (CPV) in the neutrino sector, and to resolve the mass ordering, for exposures of up to 100 kiloton-megawatt-years (kt-MW-yr). The analysis includes detailed uncertainties on the flux prediction, the neutrino interaction model, and detector effects. We demonstrate that DUNE will be able to unambiguously resolve the neutrino mass ordering at a 3$\sigma$ (5$\sigma$) level, with a 66 (100) kt-MW-yr far detector exposure, and has the ability to make strong statements at significantly shorter exposures depending on the true value of other oscillation parameters. We also show that DUNE has the potential to make a robust measurement of CPV at a 3$\sigma$ level with a 100 kt-MW-yr exposure for the maximally CP-violating values \delta_{\rm CP}} = \pm\pi/2. Additionally, the dependence of DUNE's sensitivity on the exposure taken in neutrino-enhanced and antineutrino-enhanced running is discussed. An equal fraction of exposure taken in each beam mode is found to be close to optimal when considered over the entire space of interest

Design, construction and operation of the ProtoDUNE-SP Liquid Argon TPC

The ProtoDUNE-SP detector is a single-phase liquid argon time projection chamber (LArTPC) that was constructed and operated in the CERN North Area at the end of the H4 beamline. This detector is a prototype for the first far detector module of the Deep Underground Neutrino Experiment (DUNE), which will be constructed at the Sandford Underground Research Facility (SURF) in Lead, South Dakota, USA. The ProtoDUNE-SP detector incorporates full-size components as designed for DUNE and has an active volume of $7\times 6\times 7.2$~m$^3$. The H4 beam delivers incident particles with well-measured momenta and high-purity particle identification. ProtoDUNE-SP's successful operation between 2018 and 2020 demonstrates the effectiveness of the single-phase far detector design. This paper describes the design, construction, assembly and operation of the detector components

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Comparative effectiveness and safety of non-vitamin K antagonists for atrial fibrillation in clinical practice: GLORIA-AF Registry

Background and purpose: Prospectively collected data comparing the safety and effectiveness of individual non-vitamin K antagonists (NOACs) are lacking. Our objective was to directly compare the effectiveness and safety of NOACs in patients with newly diagnosed atrial fibrillation (AF). Methods: In GLORIA-AF, a large, prospective, global registry program, consecutive patients with newly diagnosed AF were followed for 3&nbsp;years. The comparative analyses for (1) dabigatran vs rivaroxaban or apixaban and (2) rivaroxaban vs apixaban were performed on propensity score (PS)-matched patient sets. Proportional hazards regression was used to estimate hazard ratios (HRs) for outcomes of interest. Results: The GLORIA-AF Phase III registry enrolled 21,300 patients between January 2014 and December 2016. Of these, 3839 were prescribed dabigatran, 4015 rivaroxaban and 4505 apixaban, with median ages of 71.0, 71.0, and 73.0&nbsp;years, respectively. In the PS-matched set, the adjusted HRs and 95% confidence intervals (CIs) for dabigatran vs rivaroxaban were, for stroke: 1.27 (0.79–2.03), major bleeding 0.59 (0.40–0.88), myocardial infarction 0.68 (0.40–1.16), and all-cause death 0.86 (0.67–1.10). For the comparison of dabigatran vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 1.16 (0.76–1.78), myocardial infarction 0.84 (0.48–1.46), major bleeding 0.98 (0.63–1.52) and all-cause death 1.01 (0.79–1.29). For the comparison of rivaroxaban vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 0.78 (0.52–1.19), myocardial infarction 0.96 (0.63–1.45), major bleeding 1.54 (1.14–2.08), and all-cause death 0.97 (0.80–1.19). Conclusions: Patients treated with dabigatran had a 41% lower risk of major bleeding compared with rivaroxaban, but similar risks of stroke, MI, and death. Relative to apixaban, patients treated with dabigatran had similar risks of stroke, major bleeding, MI, and death. Rivaroxaban relative to apixaban had increased risk for major bleeding, but similar risks for stroke, MI, and death. Registration: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01468701, NCT01671007. Date of registration: September 2013

Anticoagulant selection in relation to the SAMe-TT2R2 score in patients with atrial fibrillation. the GLORIA-AF registry

Aim: The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores &gt;2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores &gt;2 than to patients with lower scores. Methods and results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score &gt;2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores &gt;2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores &gt;2 and 27.5% in those with scores ≤2. Conclusions: The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial. Clinical trial registration: URL: https://www.clinicaltrials.gov//Unique identifier: NCT01937377, NCT01468701, and NCT01671007