Antipsychotic medication exposure, clozapine, and pneumonia: results from a self-controlled study.

OBJECTIVE: By using a self-controlled design, we investigated whether antipsychotic medication exposure was associated with increased pneumonia risk and whether patients receiving clozapine were more likely to develop pneumonia than patients receiving other antipsychotic medications. METHODS: Through nationwide health registers, we identified all out-patients with schizophrenia initiating antipsychotic treatment. First, we estimated whether antipsychotic-naïve patients with schizophrenia increased their risk of pneumonia after initiation of either a first- or second-generation antipsychotic medication using a one-year mirror-image model. Afterward, similar analyses were made for individual second-generation antipsychotics. Lastly, the rate of pneumonia for patients initiated on clozapine was compared to patients commenced on other second-generation antipsychotics. RESULTS: In total, 8355 antipsychotic-naïve patients with schizophrenia were initiated on a first-generation antipsychotic medication; 0.95% of the patients had developed pneumonia before exposure, compared to 0.68% after exposure (P = 0.057). Similar findings were made for the 8001 antipsychotic-naïve patients with schizophrenia initiated on second-generation antipsychotic medications, with 0.56% developing pneumonia before exposure compared to 0.55% after exposure (P = 1.00). Second-generation antipsychotic medications did not increase the pneumonia risk, except for risperidone (increased by 0.32%; P = 0.007) and clozapine, which gave the largest absolute increase in pneumonia risk although not significant (increased by 0.64%; P = 0.10). The rate of pneumonia was higher after initiation of clozapine than for other second-generation antipsychotic medications. CONCLUSION: Most antipsychotic medications were not found to increase the risk of pneumonia. Clozapine exposure might be associated with increased risk of developing pneumonia.

APOE*E2 allele delays age of onset in PSEN1 E280A Alzheimer's disease.

Alzheimer's disease (AD) age of onset (ADAOO) varies greatly between individuals, with unique causal mutations suggesting the role of modifying genetic and environmental interactions. We analyzed ~50 000 common and rare functional genomic variants from 71 individuals of the 'Paisa' pedigree, the world's largest pedigree segregating a severe form of early-onset AD, who were affected carriers of the fully penetrant E280A mutation in the presenilin-1 (PSEN1) gene. Affected carriers with ages at the extremes of the ADAOO distribution (30s-70s age range), and linear mixed-effects models were used to build single-locus regression models outlining the ADAOO. We identified the rs7412 (APOE*E2 allele) as a whole exome-wide ADAOO modifier that delays ADAOO by ~12 years (ß=11.74, 95% confidence interval (CI): 8.07-15.41, P=6.31 × 10(-8), PFDR=2.48 × 10(-3)). Subsequently, to evaluate comprehensively the APOE (apolipoprotein E) haplotype variants (E1/E2/E3/E4), the markers rs7412 and rs429358 were genotyped in 93 AD affected carriers of the E280A mutation. We found that the APOE*E2 allele, and not APOE*E4, modifies ADAOO in carriers of the E280A mutation (ß=8.24, 95% CI: 4.45-12.01, P=3.84 × 10(-5)). Exploratory linear mixed-effects multilocus analysis suggested that other functional variants harbored in genes involved in cell proliferation, protein degradation, apoptotic and immune dysregulation processes (i.e., GPR20, TRIM22, FCRL5, AOAH, PINLYP, IFI16, RC3H1 and DFNA5) might interact with the APOE*E2 allele. Interestingly, suggestive evidence as an ADAOO modifier was found for one of these variants (GPR20) in a set of patients with sporadic AD from the Paisa genetic isolate. This is the first study demonstrating that the APOE*E2 allele modifies the natural history of AD typified by the age of onset in E280A mutation carriers. To the best of our knowledge, this is the largest analyzed sample of patients with a unique mutation sharing uniform environment. Formal replication of our results in other populations and in other forms of AD will be crucial for prediction, follow-up and presumably developing new therapeutic strategies for patients either at risk or affected by AD.

Robotic-assisted kidney transplantation: our first case.

PURPOSE: Kidney transplantation is the preferred treatment for patients with end-stage renal disease. In order to reduce the morbidity of the open surgery, a robotic-assisted approach has been recently introduced. According to the published literature, the robotic surgery allows the performance of kidney transplantation under optimal operative conditions while maintaining the safety and the functional results of the open approach. METHODS: We present the case of a mother donating to her daughter affected by end-stage renal disease (ESRD) due to Alport disease (creatinine: 353 umol/l; GFR: 13 ml/min per 1.73 m(2)). RESULTS: A robotic-assisted kidney transplant (RAKT) was successfully performed. Surgical time was 120 min with 53 min for vascular suture. The estimated blood loss was <50 cc. The kidney started to produce urine intra-operatively with a rate of 250 cc/h, which remained constant over the next hours. During the first postoperative day, the patient was ambulating and started oral intake. Pain was minimal, and no analgesia was required after 48 h. Serum creatinine improved progressively to 89 umol/l on postoperative day 3. No surgical complications were recorded, and the patient was sent home on postoperative day 5. CONCLUSION: We present the first Spanish transperitoneal pure RAKT from a living-related donor. We believe this is the second pure robotic-assisted kidney transplantation case performed in Europe. We believe that the potential advantages of RAKT are related to the quality of the vascular anastomosis, the possible lower complication rate and the shorter recovery of the recipients.

Trajectories of symptom dimensions in short-term response to antipsychotic treatment in patients with a first episode of non-affective psychosis.

BACKGROUND: Trajectory patterns of positive, disorganized and negative dimension symptoms during antipsychotic treatment in drug-naive patients with first-episode psychosis have yet to be examined by using naturalistic data. METHOD: This pragmatic clinical trial randomized 161 drug-naive patients with a first episode of psychosis to olanzapine, risperidone or haloperidol. Patients were assessed with the Scale for the Assessment of Negative Symptoms (SANS) and Positive Symptoms (SAPS) at baseline and at the end of weeks 1, 2, 3, 4 and 6 of antipsychotic treatment. Censored normal models of response trajectories were developed with three dimensions of the SAPS-SANS scores (positive, disorganized and negative) in order to identify the different response trajectories. Diagnosis, cannabis use, duration of untreated psychosis (DUP), smoking and antipsychotic class were examined as possible predictive variables. RESULTS: Patients were classified in five groups according to the positive dimension, three groups according to the disorganized dimension and five groups according to the negative dimension. Longer DUPs and cannabis use were associated with higher scores and poorer responses in the positive dimension. Cannabis use was associated with higher scores and poorer responses in the disorganized dimension. Only schizophrenia diagnosis was associated with higher scores and poorer responses in the negative dimension. CONCLUSIONS: Our results illustrate the heterogeneity of short-term response to antipsychotics in patients with a first episode of psychosis and highlight markedly different patterns of response in the positive, disorganized and negative dimensions. DUP, cannabis use and diagnosis appeared to have a prognostic value in predicting treatment response with different implications for each dimension.

Can valproic acid be an inducer of clozapine metabolism?

INTRODUCTION: Prior clozapine studies indicated no effects, mild inhibition or induction of valproic acid (VPA) on clozapine metabolism. The hypotheses that (i) VPA is a net inducer of clozapine metabolism, and (ii) smoking modifies this inductive effect were tested in a therapeutic drug monitoring study. METHODS: After excluding strong inhibitors and inducers, 353 steady-state total clozapine (clozapine plus norclozapine) concentrations provided by 151 patients were analyzed using a random intercept linear model. RESULTS: VPA appeared to be an inducer of clozapine metabolism since total plasma clozapine concentrations in subjects taking VPA were significantly lower (27% lower; 95% confidence interval, 14-39%) after controlling for confounding variables including smoking (35% lower, 28-56%). DISCUSSION: Prospective studies are needed to definitively establish that VPA may (i) be an inducer of clozapine metabolism when induction prevails over competitive inhibition, and (ii) be an inducer even in smokers who are under the influence of smoking inductive effects on clozapine metabolism.

Facile one-pot synthesis of lithium metal nanoparticles for superior lithium-ion anode applications.

A capable one-step method, femtosecond laser ablation of solids in liquids, was successfully applied to prepare lithium metal nanoparticles to mitigate the initial capacity loss and improve the electrochemical performance of a graphite-based electrode as a Li-host anode. Remarkably, according to the physicochemical characterization, this advanced optical method allowed to obtain uniform spheroidal and crystalline Li nanoparticles with an average particle size <20 nm. These novel ultrafine Li nanoparticles significantly decrease the initial capacity loss of a graphite-based anode, leading to reach high coulombic efficiency (>99 %), good specific charge capacity (322 mAh/g), and superior capacity retention (96 %) at an applied current density of 100 mA g-1 after 200 cycles.

[Ambulatory blood pressure monitoring, adult and pediatric population. A narrative review]. / Monitorización ambulatoria de la presión arterial en adultos y población pediátrica. Una revisión narrativa.

Hypertension has become a central risk factor for the development of cardiovascular disease, underscoring the importance of its accurate diagnosis. Numerous studies have established a close relationship between elevated systolic (SBP) and diastolic (DBP) blood pressure and an increased risk of cardiovascular event (CVE). Traditionally, blood pressure (BP) measurements performed in clinical settings have been the main method for diagnosing and assessing hypertension. However, in recent years, it has been recognized that BP measurements obtained outside the clinical setting, using self-monitoring blood pressure (SMBP) and ambulatory blood pressure monitoring (ABPM), offer a more realistic perspective of patients' daily lives and therefore provide more reliable results. Given the evolution of medical devices, diagnostic criteria, and the increasing relevance of certain components of ABPM in the prediction of adverse cardiovascular outcomes, a comprehensive update that is practical for daily clinical practice is required. The main objective of this article is to provide an updated review of ABPM, focusing on its importance in the evaluation of hypertension and its impact on public health in Colombia. In addition, it will discuss the implications of changes in diagnostic thresholds and provide concrete recommendations for the effective implementation of ABPM in clinical practice, allowing health professionals to make informed decisions and improve the care of their patients.

Profiles of mathematical deficits in children with dyslexia.

Despite a high rate of concurrent mathematical difficulties among children with dyslexia, we still have limited information regarding the prevalence and severity of mathematical deficits in this population. To address this gap, we developed a comprehensive battery of cognitive tests, known as the UCSF Mathematical Cognition Battery (MCB), with the aim of identifying deficits in four distinct mathematical domains: number processing, arithmetical procedures, arithmetic facts retrieval, and geometrical abilities. The mathematical abilities of a cohort of 75 children referred to the UCSF Dyslexia Center with a diagnosis of dyslexia, along with 18 typically developing controls aged 7 to 16, were initially evaluated using a behavioral neurology approach. A team of professional clinicians classified the 75 children with dyslexia into five groups, based on parents' and teachers' reported symptoms and clinical history. These groups included children with no mathematical deficits and children with mathematical deficits in number processing, arithmetical procedures, arithmetic facts retrieval, or geometrical abilities. Subsequently, the children underwent evaluation using the MCB to determine concordance with the clinicians' impressions. Additionally, neuropsychological and cognitive standardized tests were administered. Our study reveals that within a cohort of children with dyslexia, 66% exhibit mathematical deficits, and among those with mathematical deficits, there is heterogeneity in the nature of these deficits. If these findings are confirmed in larger samples, they can potentially pave the way for new diagnostic approaches, consistent subtype classification, and, ultimately personalized interventions.

Effects of non-pharmacological therapy on normal ageing and on cognitive decline: reflections on treatment objectives.

INTRODUCTION: Non-pharmacological therapies for normal ageing and dementia are a set of treatment programmes intended to improve the performance of cognitive processes, improve emotional well-being, promote independence in daily life activities, and ultimately increase patients' quality of life. METHODS: We applied a battery of tests assessing four major domains (general mental state, emotional well-being, quality of life, and daily life activities) to a sample of 317 adults older than 64 (240 with normal ageing and 77 with cognitive impairment). They were then assigned either to non-pharmacological therapy groups according to their abilities or to other non-specific activities. Progress was assessed 9 months later using the same test battery. RESULTS: The results show a general improvement in mental state in the group with normal ageing and absence of disease progression in the group with pathological ageing. In both groups, emotional well-being (anxiety and depression) and self-identified quality of life both benefited from non-pharmacological therapy. However, other aspects commonly included among the therapeutic targets did not seem to improve, including independence in daily life activities. CONCLUSIONS: This study provides evidence that non-pharmacological therapy in ageing patients can produce positive results. It must be stressed that benefits are greater in individuals with cognitive impairment, although generalising use of this therapy could prove to be an excellent primary programme for preventing cognitive and emotional disorders.

[Ten years of the prefrontal symptoms inventory (PSI). A systematic review]. / Diez años del inventario de síntomas prefrontales (ISP). Una revisión sistemática.

INTRODUCTION: Ten years ago, Revista de Neurologia published the validation of a new free tool: the Prefrontal Symptoms Inventory (PSI), from which an abbreviated version (PSI-20) was subsequently extracted. Over this decade, authors have demonstrated its excellent psychometric properties and clinical usefulness. This systematic review, conducted in accordance with the PRISMA statement, aims to analyse the body of research that has used the PSI or PSI-20 in order to assess its relevance in other research teams, other clinical populations and even other cultures. MATERIALS AND METHODS: A search was conducted to find articles written in Spanish, English, French and Portuguese that have used the inventory to carry out empirical research. Finally, 56 articles were selected. RESULTS: The results show that the PSI and the PSI-20 have been widely used in Spain as well as in other Spanish-speaking countries (Argentina, Chile, Colombia, Cuba, Ecuador or Venezuela) and employed to a moderate extent in non-Spanish-speaking countries (Belgium, Brazil, Sweden or Switzerland). The clinical populations in which they have been used range from acquired brain injury and degenerative dementias to chronic pain, fibromyalgia, addictive behaviours or personality disorders. Given their versatility, they have also been used with the general population, including prison inmates, women in rural areas, university students or to study cognitive reserve. CONCLUSIONS: The PSI and PSI-20 are useful instruments for research and clinical use, and the next challenge is to validate an English version, which is currently being worked on.

TITLE: Diez años del inventario de síntomas prefrontales (ISP). Una revisión sistemática.Introducción. Hace 10 años, Revista de Neurología publicaba la validación de una nueva herramienta gratuita: el inventario de síntomas prefrontales (ISP), de la que posteriormente se extrajo su versión abreviada (ISP-20). Durante esta década, los autores han acreditado sus excelentes propiedades psicométricas y su utilidad clínica. La presente revisión sistemática, sometida a la declaración PRISMA, tiene el objetivo de analizar el corpus de investigación que ha utilizado el ISP o el ISP-20, para valorar su trascendencia en otros equipos de investigación, en otras poblaciones clínicas e incluso en otras culturas. Materiales y métodos. Se buscaron artículos que hayan utilizado el inventario para realizar trabajos empíricos, en español, inglés, francés y portugués. Finalmente, se seleccionaron 56 trabajos. Resultados. Los resultados muestran que el ISP y el ISP-20 han tenido un uso elevado en España, así como en otros países de habla hispana (Argentina, Chile, Colombia, Cuba, Ecuador o Venezuela), y un uso moderado en países de habla no hispana (Bélgica, Brasil, Suecia o Suiza). Las poblaciones clínicas en las que se han utilizado abarcan desde el daño cerebral adquirido y las demencias degenerativas hasta el dolor crónico, la fibromialgia, las conductas adictivas o los trastornos de la personalidad. Dada su versatilidad, también se han usado con población general, incluyendo población reclusa, mujeres en entorno rural, estudiantes universitarios o para el estudio de la reserva cognitiva. Conclusiones. El ISP y el ISP-20 son instrumentos útiles para la investigación y la clínica, cuyo siguiente desafío es la validación de una versión en inglés, en la que se está trabajando.

Tools for optimising pharmacotherapy in psychiatry (therapeutic drug monitoring, molecular brain imaging and pharmacogenetic tests): focus on antidepressants.

Objectives: More than 40 drugs are available to treat affective disorders. Individual selection of the optimal drug and dose is required to attain the highest possible efficacy and acceptable tolerability for every patient.Methods: This review, which includes more than 500 articles selected by 30 experts, combines relevant knowledge on studies investigating the pharmacokinetics, pharmacodynamics and pharmacogenetics of 33 antidepressant drugs and of 4 drugs approved for augmentation in cases of insufficient response to antidepressant monotherapy. Such studies typically measure drug concentrations in blood (i.e. therapeutic drug monitoring) and genotype relevant genetic polymorphisms of enzymes, transporters or receptors involved in drug metabolism or mechanism of action. Imaging studies, primarily positron emission tomography that relates drug concentrations in blood and radioligand binding, are considered to quantify target structure occupancy by the antidepressant drugs in vivo. Results: Evidence is given that in vivo imaging, therapeutic drug monitoring and genotyping and/or phenotyping of drug metabolising enzymes should be an integral part in the development of any new antidepressant drug.Conclusions: To guide antidepressant drug therapy in everyday practice, there are multiple indications such as uncertain adherence, polypharmacy, nonresponse and/or adverse reactions under therapeutically recommended doses, where therapeutic drug monitoring and cytochrome P450 genotyping and/or phenotyping should be applied as valid tools of precision medicine.

A nearby transiting rocky exoplanet that is suitable for atmospheric investigation.

Spectroscopy of transiting exoplanets can be used to investigate their atmospheric properties and habitability. Combining radial velocity (RV) and transit data provides additional information on exoplanet physical properties. We detect a transiting rocky planet with an orbital period of 1.467 days around the nearby red dwarf star Gliese 486. The planet Gliese 486 b is 2.81 Earth masses and 1.31 Earth radii, with uncertainties of 5%, as determined from RV data and photometric light curves. The host star is at a distance of ~8.1 parsecs, has a J-band magnitude of ~7.2, and is observable from both hemispheres of Earth. On the basis of these properties and the planet's short orbital period and high equilibrium temperature, we show that this terrestrial planet is suitable for emission and transit spectroscopy.

Variations in color and reflectance on the surface of asteroid (101955) Bennu.

Visible-wavelength color and reflectance provide information about the geologic history of planetary surfaces. Here we present multispectral images (0.44 to 0.89 micrometers) of near-Earth asteroid (101955) Bennu. The surface has variable colors overlain on a moderately blue global terrain. Two primary boulder types are distinguishable by their reflectance and texture. Space weathering of Bennu surface materials does not simply progress from red to blue (or vice versa). Instead, freshly exposed, redder surfaces initially brighten in the near-ultraviolet region (i.e., become bluer at shorter wavelengths), then brighten in the visible to near-infrared region, leading to Bennu's moderately blue average color. Craters indicate that the time scale of these color changes is ~105 years. We attribute the reflectance and color variation to a combination of primordial heterogeneity and varying exposure ages.

High-Temperature XAS Study of Fe2SiO4 Liquid: Reduced Coordination of Ferrous Iron.

X-ray absorption spectroscopy (XAS) of Fe(2+) in Fe(2)SiO(4) liquid at 1575 kelvin and 10(-4) gigapascal (1 bar) shows that the Fe(2+) -O bond length is 1.98 +/- 0.02 angstroms compared with approximately 2.22 angstroms in crystalline Fe(2)SiO(4) (fayalite) at the melting point (1478 kelvin), which indicates a decrease in average Fe(2+) coordination number from six in fayalite to four in the liquid. Anharmonicity in the liquid was accounted for using a data analysis procedure. This reduction in coordination number is similar to that observed on the melting of certain ionic salts. These results are used to develop a model of the medium-range structural environment of Fe(2+) in olivine-composition melts, which helps explain some of the properties of Fe(2)SiO(4) liquid, including density, viscosity, and the partitioning of iron and nickel between silicate melts and crystalline olivines. Some of the implications of this model for silicate melts in the Earth's crust and mantle are discussed.

Severity of personality disorders and suicide attempt.

OBJECTIVE: Severity of personality disorders (PDs) may be more useful in estimating suicide risk than the diagnosis of specific PDs. We hypothesized that suicide attempters with severe PD would present more attempts and attempts of greater severity/lethality. METHOD: Four hundred and forty-six suicide attempters were assessed. PD diagnosis was made using the International Personality Disorder Questionnaire--Screening Questionnaire. PDs were classified using Tyrer and Johnson's classification of severity (no PD, simple PD, diffuse PD). Severity/lethality of attempts was measured with the Suicide Intent Scale, Risk-Rescue Rating Scale and Lethality Rating Scale. RESULTS: Attempters with severe (diffuse) PD had more attempts than the other groups. After controlling for age and gender, this difference remained significant only for the younger age group and women. There was no relationship between severity of PDs and severity/lethality of attempts. CONCLUSION: Younger female attempters with severe PD are prone to repeated attempts. However, the severity of PD was not related to the severity/lethality of suicide attempts.

Idiopathic thoracic aortic aneurysm at pediatric age.

A 6-year-old-boy presented with epigastric pain and vomiting over 1 year. Chest X-ray and esophagogastric transit showed a mediastinal mass. A chest computerized tomography angiogram demonstrated a descending thoracic aortic aneurysm. Analytical determinations carried out were all negative. The aneurysm was surgically repaired using a Dacron patch. The anatomopathological study described atherosclerotic lesions with calcifications, compatible with an atherosclerotic aneurysm wall. Aneurysms are uncommon in the pediatric population. Usually, no pathogenesis can be determined, and thus, such cases are grouped as idiopathic. Direct repair with or without patch is a therapeutic alternative in pediatric aneurysms and can allow the growth of the aortic circumference.

Fagerstrom test for nicotine dependence vs heavy smoking index in a general population survey.

BACKGROUND: The Fagerström Test for Nicotine Dependence (FTND) is used for assessing nicotine dependence. A shorter test derived from the FTND used for the general population is the Heavy Smoking Index (HSI) (six questions vs. two). The objective of this study is to compare the validity of the HSI versus the FTND. METHODS: A survey of tobacco use in the general population was carried out in the northern Spanish region of Galicia using both the FTND and the HSI to study a representative sample of 1655 daily smokers. The HSI was compared with the FTND, considered the gold standard. Measures of sensitivity, specificity and predictive values were calculated. Concordance between the tests was also established (Cohen's kappa). RESULTS: Cohen's kappa showed good agreement between measures (Kappa = 0.7); specificity values were also high (Sp = 96.2%). Sensitivity analysis in females (Se = 62.3%) did not show good agreement. CONCLUSIONS: The HSI can be used as a reasonably good screening test in order to identify daily smokers with high nicotine dependence. Nevertheless, for populations or subpopulations having low nicotine dependence, such as women, the FTND is more reliable.