Population pharmacokinetic and pharmacodynamic properties of intramuscular quinine in Tanzanian children with severe Falciparum malaria.

Although artesunate is clearly superior, parenteral quinine is still used widely for the treatment of severe malaria. A loading-dose regimen has been recommended for 30 years but is still often not used. A population pharmacokinetic study was conducted with 75 Tanzanian children aged 4 months to 8 years with severe malaria who received quinine intramuscularly; 69 patients received a loading dose of 20 mg quinine dihydrochloride (salt)/kg of body weight. Twenty-one patients had plasma quinine concentrations detectable at baseline. A zero-order absorption model with one-compartment disposition pharmacokinetics described the data adequately. Body weight was the only significant covariate and was implemented as an allometric function on clearance and volume parameters. Population pharmacokinetic parameter estimates (and percent relative standard errors [%RSE]) of elimination clearance, central volume of distribution, and duration of zero-order absorption were 0.977 liters/h (6.50%), 16.7 liters (6.39%), and 1.42 h (21.5%), respectively, for a typical patient weighing 11 kg. Quinine exposure was reduced at lower body weights after standard weight-based dosing; there was 18% less exposure over 24 h in patients weighing 5 kg than in those weighing 25 kg. Maximum plasma concentrations after the loading dose were unaffected by body weight. There was no evidence of dose-related drug toxicity with the loading dosing regimen. Intramuscular quinine is rapidly and reliably absorbed in children with severe falciparum malaria. Based on these pharmacokinetic data, a loading dose of 20 mg salt/kg is recommended, provided that no loading dose was administered within 24 h and no routine dose was administered within 12 h of admission. (This study has been registered with Current Controlled Trials under registration number ISRCTN 50258054.)

Anisotropic Superparamagnetism of Monodispersive Cobalt-Platinum Nanocrystals

Based on the high-temperature organometallic route (Sun et al. Science 287, 1989 (2000)), we have synthesized powders containing CoPt_3 single crystals with mean diameters of 3.3(2) nm and 6.0(2) nm and small log-normal widths sigma=0.15(1). In the entire temperature range from 5 K to 400 K, the zero-field cooled susceptibility chi(T) displays significant deviations from ideal superparamagnetism. Approaching the Curie temperature of 450(10) K, the deviations arise from the (mean-field) type reduction of the ferromagnetic moments, while below the blocking temperature T_b, chi(T) is suppressed by the presence of energy barriers, the distributions of which scale with the particle volumes obtained from transmission electron microscopy (TEM). This indication for volume anisotropy is supported by scaling analyses of the shape of the magnetic absorption chi''(T,omega) which reveal distribution functions for the barriers being also consistent with the volume distributions observed by TEM. Above 200 K, the magnetization isotherms M(H,T) display Langevin behavior providing 2.5(1) mu_B per CoPt_3 in agreement with reports on bulk and thin film CoPt_3. The non-Langevin shape of the magnetization curves at lower temperatures is for the first time interpreted as anisotropic superparamagnetism by taking into account an anisotropy energy of the nanoparticles E_A(T). Using the magnitude and temperature variation of E_A(T), the mean energy barriers and 'unphysical' small switching times of the particles obtained from the analyses of chi''(T,omega) are explained. Below T_b hysteresis loops appear and are quantitatively described by a blocking model, which also ignores particle interactions, but takes the size distributions from TEM and the conventional field dependence of E_A into account.Comment: 12 pages with 10 figures and 1 table. Version accepted for publication in Phys. Rev. B . Two-column layou

Thinking inside the box:improving the lifestyle of inpatients with severe mental illness

BACKGROUND: An unhealthy lifestyle plays an important role in the substantially reduced life-expectancy of inpatients with severe mental illness (SMI). However, there is a lack of evidence on the long-term effectiveness and implementation of lifestyle improvements in inpatient mental healthcare.&lt;br/&gt; AIM: Increasing knowledge and understanding of (the implementation of) lifestyle changes in inpatients with SMI in longer-term clinical care.&lt;br/&gt; METHOD: Cross-sectional research followed by an observational study to evaluate a multidisciplinary lifestyle enhancing treatment (MULTI) for both changes in health-related outcomes after 18 months compared to treatment as usual (TAU), and the implementation barriers and facilitators.&lt;br/&gt; RESULTS: Patients were very sedentary and less physically active compared to people without SMI. After 18 months, MULTI showed significant improvements in total physical activity, cardiometabolic risk factors, psychosocial functioning and mediation use, compared to TAU. Physical health did not improve in TAU. The implementation of MULTI was hampered by organisational factors and facilitated by positive attitudes of healthcare professionals and patients towards MULTI and their own role in it.&lt;br/&gt; CONCLUSION: Using a multidisciplinary integrated approach, it is possible to improve the lifestyle, and thus the health status, of SMI inpatients, within the current context of routine mental healthcare.</p

Thinking inside the box:improving the lifestyle of inpatients with severe mental illness

BACKGROUND: An unhealthy lifestyle plays an important role in the substantially reduced life-expectancy of inpatients with severe mental illness (SMI). However, there is a lack of evidence on the long-term effectiveness and implementation of lifestyle improvements in inpatient mental healthcare.&lt;br/&gt; AIM: Increasing knowledge and understanding of (the implementation of) lifestyle changes in inpatients with SMI in longer-term clinical care.&lt;br/&gt; METHOD: Cross-sectional research followed by an observational study to evaluate a multidisciplinary lifestyle enhancing treatment (MULTI) for both changes in health-related outcomes after 18 months compared to treatment as usual (TAU), and the implementation barriers and facilitators.&lt;br/&gt; RESULTS: Patients were very sedentary and less physically active compared to people without SMI. After 18 months, MULTI showed significant improvements in total physical activity, cardiometabolic risk factors, psychosocial functioning and mediation use, compared to TAU. Physical health did not improve in TAU. The implementation of MULTI was hampered by organisational factors and facilitated by positive attitudes of healthcare professionals and patients towards MULTI and their own role in it.&lt;br/&gt; CONCLUSION: Using a multidisciplinary integrated approach, it is possible to improve the lifestyle, and thus the health status, of SMI inpatients, within the current context of routine mental healthcare.</p

Comparative analysis between condom use clusters and risk behaviours among portuguese university students

The research on condom use has been focused on high-risk individuals, paying less attention to those who have moderate risk or safe sexual conducts. In order to design accurate interventions, potential differences among the condom use behavior groups must be considered. The goal was to assess possible differences in individuals presenting different types of risk behavior. 140 heterosexual university students answered a self-reported questionnaire about their sexual history, condom use habits, sexual self-esteem, sexual satisfaction, sexual control, attitudes towards condoms, self-efficacy to condom use, and emotions and feelings during sexual intercourse. A cluster analysis was conducted using the results about condom use and risk behaviors. Three groups with different risk levels emerged, presenting differences over sexual self-efficacy, attitudes towards condoms, socio-demographic variables, and sexual history. The results suggest the condom use inconsistency is highly associated with other risk behaviors but the contrary does not necessarily happens. Condom use consistent users also presented risk behaviors as smoking and drinking. The group differences suggest the risks were more affected by the combination of lack of skills with a negative attitude toward condoms than by contextual or personal variables. These differences sustain the need of an intervention adjusted to the individual's risk levels, since they differ on skills and beliefs that may hinder or promote the adoption of health behaviors.Foundation for Science and Technology/Fundacao para a Ciencia e Tecnologia (Portugal)info:eu-repo/semantics/publishedVersio

Subjective cognitive decline and self-reported sleep problems: The SCIENCe project

We aim to investigate the frequency and type of sleep problems in memory clinic patients with subjective cognitive decline (SCD) and their association with cognition, mental health, brain magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) biomarkers. Three hundred eight subjects (65 ± 8 years, 44% female) were selected from the Subjective Cognitive Impairment Cohort (SCIENCe) project. All subjects answered two sleep questionnaires, Berlin Questionnaire (sleep apnea) and Pittsburgh Sleep Quality Index (sleep quality) and underwent a standardized memory clinic work-up. One hundred ninety-eight (64%) subjects reported sleep problems, based on 107 (35%) positive screenings on sleep apnea and 162 (53%) on poor sleep quality. Subjects with sleep problems reported more severe depressive symptoms, more anxiety, and more severe SCD. Cognitive tests, MRI, and CSF biomarkers did not differ between groups. Our results suggest that improvement of sleep quality and behaviors are potential leads for treatment in many subjects with SCD to relieve the experienced cognitive complaints

Sex differences associated with adverse drug reactions resulting in hospital admissions

Background Adverse drug events, including adverse drug reactions (ADRs), are responsible for approximately 5% of unplanned hospital admissions: a major health concern. Women are 1.5-1.7 times more likely to develop ADRs. The main objective was to identify sex differences in the types and number of ADRs leading to hospital admission. Methods ADR-related hospital admissions between 2005 and 2017 were identified from the PHARMO Database Network using hospital discharge diagnoses. Patients aged >= 16 years with a drug possibly responsible for the ADR and dispensed within 3 months before admission were included. Age-adjusted odds ratios (OR) with 95% CIs for drug-ADR combinations for women versus men were calculated. Results A total of 18,469 ADR-related hospital admissions involving women (0.35% of all women admitted) and 14,678 admissions involving men (0.35% of all men admitted) were included. Most substantial differences were seen in ADRs due to anticoagulants and diuretics. Anticoagulants showed a lower risk of admission with persistent haematuria (ORadj 0.31; 95%CI 0.21, 0.45) haemoptysis (ORadj 0.47, 95%CI 0.30,0.74) and subdural haemorrhage (ORadj 0.61; 95%CI 0.42,0.88) in women than in men and a higher risk of rectal bleeding in women (ORadj 1.48; 95%CI 1.04,2.11). Also, there was a higher risk of admission in women using thiazide diuretics causing hypokalaemia (ORadj 3.03; 95%CI 1.58, 5.79) and hyponatraemia (ORadj 3.33, 95%CI 2.31, 4.81) than in men. Conclusions There are sex-related differences in the risk of hospital admission in specific drug-ADR combinations. The most substantial differences were due to anticoagulants and diuretics.Peer reviewe

Effects of boundary conditions on magnetization switching in kinetic Ising models of nanoscale ferromagnets

Magnetization switching in highly anisotropic single-domain ferromagnets has been previously shown to be qualitatively described by the droplet theory of metastable decay and simulations of two-dimensional kinetic Ising systems with periodic boundary conditions. In this article we consider the effects of boundary conditions on the switching phenomena. A rich range of behaviors is predicted by droplet theory: the specific mechanism by which switching occurs depends on the structure of the boundary, the particle size, the temperature, and the strength of the applied field. The theory predicts the existence of a peak in the switching field as a function of system size in both systems with periodic boundary conditions and in systems with boundaries. The size of the peak is strongly dependent on the boundary effects. It is generally reduced by open boundary conditions, and in some cases it disappears if the boundaries are too favorable towards nucleation. However, we also demonstrate conditions under which the peak remains discernible. This peak arises as a purely dynamic effect and is not related to the possible existence of multiple domains. We illustrate the predictions of droplet theory by Monte Carlo simulations of two-dimensional Ising systems with various system shapes and boundary conditions.Comment: RevTex, 48 pages, 13 figure

Ab initio atomistic thermodynamics and statistical mechanics of surface properties and functions

Previous and present "academic" research aiming at atomic scale understanding is mainly concerned with the study of individual molecular processes possibly underlying materials science applications. Appealing properties of an individual process are then frequently discussed in terms of their direct importance for the envisioned material function, or reciprocally, the function of materials is somehow believed to be understandable by essentially one prominent elementary process only. What is often overlooked in this approach is that in macroscopic systems of technological relevance typically a large number of distinct atomic scale processes take place. Which of them are decisive for observable system properties and functions is then not only determined by the detailed individual properties of each process alone, but in many, if not most cases also the interplay of all processes, i.e. how they act together, plays a crucial role. For a "predictive materials science modeling with microscopic understanding", a description that treats the statistical interplay of a large number of microscopically well-described elementary processes must therefore be applied. Modern electronic structure theory methods such as DFT have become a standard tool for the accurate description of individual molecular processes. Here, we discuss the present status of emerging methodologies which attempt to achieve a (hopefully seamless) match of DFT with concepts from statistical mechanics or thermodynamics, in order to also address the interplay of the various molecular processes. The new quality of, and the novel insights that can be gained by, such techniques is illustrated by how they allow the description of crystal surfaces in contact with realistic gas-phase environments.Comment: 24 pages including 17 figures, related publications can be found at http://www.fhi-berlin.mpg.de/th/paper.htm