The high arithmetic performance and intrinsic parallelism of recent graphical processing units (GPUs) can offer a technological edge for molecular dynamics simulations. ACEMD is a production-class ...biomolecular dynamics (MD) engine supporting CHARMM and AMBER force fields. Designed specifically for GPUs it is able to achieve supercomputing scale performance of 40 ns/day for all-atom protein systems with over 23 000 atoms. We provide a validation and performance evaluation of the code and run a microsecond-long trajectory for an all-atom molecular system in explicit TIP3P water on a single workstation computer equipped with just 3 GPUs. We believe that microsecond time scale molecular dynamics on cost-effective hardware will have important methodological and scientific implications.
Introduction
Despite the widespread use of long-acting injectable (LAI) antipsychotics in schizophrenia and other disorders, there is a lack of longitudinal studies evaluating prescription trends and ...the usefulness of therapeutic drug monitoring (TDM) to inform dosing. Indeed, LAI prescription varies greatly among different areas of the world and over the years.
Objectives
Assess trends in LAI prescription in 2013-2020 at the Psychiatry Department of Bozen, Italy, and (2) analyze the correlation between dose of prescribed LAIs and blood levels measured via TDM.
Methods
Parametric statistics.
Results
LAIs were administered to 471 patients (x̅ age±SD=47.2±16.3 years; 56.3% men). The pie chart shows LAI treatment duration, i.e., from 1 to 7 consecutive years. The most used LAIs were haloperidol in 2013-2104 (26.5-31.8%) and paliperidone in 2015-2020 (22.5-25.7%). Dose adjustments were rather frequent, whereas the switch between LAI, due to moderate-to-side effects or unsatisfactory improvement of clinical status, was infrequent (41 cases/8 years). LAI interruption for the same reasons or non-compliance was even more infrequent (10 cases), but in 8 cases it happened for opposite reasons, i.e., achievement of patients’ stabilization and good compliance. The Table shows doses and plasma levels of LAIs. Correlations between doses and plasma levels were: haloperidol: r=-0.037, p=0.620; paliperidone: r=0.290; p=0.000; risperidone: r=0.219, p=0.006; fluphenazine r=0.358, p=0.000; aripiprazole: r=-0.051, p=0.610; olanzapine: r=-0.090, p=0.634.
Conclusions
Haloperidol and paliperidone were the most used LAIs. Drug prescription trends and doses were stable over time. A significant positive correlation between dose and plasma level was found for paliperidone, fluphenazine, and aripiprazole.
Disclosure
No significant relationships.
Objective:To identify the most frequent gender-specific suicide methods in Europe.Design:Proportions of seven predominant suicide methods utilised in 16 countries participating in the European ...Alliance Against Depression (EAAD) were reported in total and cross-nationally. Relative risk (RR) relating to suicide methods and gender was calculated. To group countries by pattern of suicide methods, hierarchical clustering was applied.Setting and participants:Data on suicide methods for 119 122 male and 41 338 female cases in 2000–4/5 from 16 EAAD countries, covering 52% of European population were obtained.Results:Hanging was the most prevalent suicide method among both males (54.3%) and females (35.6%). For males, hanging was followed by firearms (9.7%) and poisoning by drugs (8.6%); for females, by poisoning by drugs (24.7%) and jumping from a high place (14.5%). Only in Switzerland did hanging rank as second for males after firearms. Hanging ranked first among females in eight countries, poisoning by drugs in five and jumping from a high place in three. In all countries, males had a higher risk than females of using firearms and hanging and a lower risk of poisoning by drugs, drowning and jumping. Grouping showed that countries might be divided into five main groups among males; for females, grouping did not yield clear results.Conclusions:Research on suicide methods could lead to the development of gender-specific intervention strategies. Nevertheless, other approaches, such as better identification and treatment of mental disorders and the improvement of toxicological aid should be put in place.
Sexual dysfunction is a potential side effect of antidepressant drugs: this article presents a critical review of the current literature. Although many studies have been published on this subject, ...only some have used a validated sexual function rating scale and most lacked either a baseline or placebo control or both. In addition, many of the studies on sexual dysfunction associated with antidepressants are limited by other methodological flaws. However, there is consistent evidence to suggest that antidepressant medication adversely affects one or more of the 3 phases of sexual response (desire, arousal and orgasm). Antidepressants with strong serotonergic properties have the highest rate of sexual side effects. Clinicians must be aware of drug-induced sexual dysfunction, since its presence can have important consequences on clinical management and compliance.
Sexual dysfunction is a potential side effect of antipsychotic drugs: this article presents a critical review of the current literature. Although many studies have been published on the subject, only ...some used a validated sexual function rating scale and most lacked either a baseline or placebo control or both. In addition, many of the studies on sexual dysfunction associated with antipsychotic medication are limited by other methodological flaws. However, there is consistent evidence to suggest that a large number of antipsychotic drugs adversely affect one or more of the 3 phases of sexual response (desire, arousal and orgasm). Among the antipsychotics, the so called "prolactin-raising" are probably most associated with sexual dysfunction, even if further studies to confirm this are needed: the reviewed literature shows no consistent evidence that any one antipsychotic drug has a significantly superior side effect profile over another and current information on this topic is often based on methodologically weak research. Clinicians must be aware of drug-induced sexual dysfunction, since its presence can have important consequences for clinical management and compliance.
Sexual dysfunction is a potential side effect of cardiovascular drugs: this article is a critical review of the current literature. Many studies have been published on this topic. Most of these ...studies are not methodologically robust, few are RCTs and most did not use a validated rating scale to evaluate sexual functioning. In addition, other methodological flaws limit greatly the conclusions of these studies. Most studies relate to male populations and only a few have been conducted on women. Also, the majority of studies on sexual dysfunction induced by cardiovascular drugs relate to antihypertensive drugs. While there is evidence to suggest that older antihypertensive drugs (diuretics, beta-blockers, centrally acting agents) have a negative impact on erectile function, newer agents seem to have either neutral (ACE inhibitors, calcium antagonists) or beneficial effects (i. e., angiotensin receptor blockers, nebivolol). Other cardiovascular drugs analyzed in this review also appear to have an inhibitory action on sexual function. For men, there is some weak evidence supporting the use of specific treatment strategies for sexual dysfunction associated with these drugs.
This study was conducted in 2014 using the paper and electronic resources of the library of the "Azienda Provinciale per i Servizi Sanitari (APSS)" in Trento, Italy (http://atoz.ebsco.com/Titles/2793). The library has access to a wide range of databases including DYNAMED, MEDLINE Full Text, CINAHL Plus Full Text, The Cochrane Library, Micromedex healthcare series, BMJ Clinical Evidence. The full list of available journals can be viewed at http://atoz.ebsco.com/Titles/2793 or at the APSS web site (http://www.apss.tn.it). In completing this review, a literature search was conducted using the key words "cardiovascular", "adrenergic beta antagonist", "α1-adrenoceptor antagonist", "angiotensin converting enzyme inhibitor", "angiotensin receptor antagonist", "angiotensin receptor blocker", "beta blocker", "beta receptor antagonist", "calcium channel blocker", "diuretic", "antihypertensive", "sexual dysfunction", "sexual side effects", "treatment-emergent sexual dysfunction". All resulting listed articles were reviewed.
The review includes studies that investigated the relationship between these drug treatments and sexual dysfunction. The purpose was to identify possible intervention strategies for sexual dysfunction related to these drugs.
The recent introduction of cost-effective accelerator processors (APs), such as the IBM Cell processor and Nvidia's graphics processing units (GPUs), represents an important technological innovation ...which promises to unleash the full potential of atomistic molecular modeling and simulation for the biotechnology industry. Present APs can deliver over an order of magnitude more floating-point operations per second (flops) than standard processors, broadly equivalent to a decade of Moore's law growth, and significantly reduce the cost of current atom-based molecular simulations. In conjunction with distributed and grid-computing solutions, accelerated molecular simulations may finally be used to extend current
in silico protocols by the use of accurate thermodynamic calculations instead of approximate methods and simulate hundreds of protein–ligand complexes with full molecular specificity, a crucial requirement of
in silico drug discovery workflows.
We present a hybrid computational method for simulating the dynamics of macromolecules in solution which couples a mesoscale solver for the fluctuating hydrodynamics (FH) equations with molecular ...dynamics to describe the macromolecule. The two models interact through a dissipative Stokesian term first introduced by Ahlrichs and Dunweg J. Chem. Phys. 111, 8225 (1999). We show that our method correctly captures the static and dynamical properties of polymer chains as predicted by the Zimm model. In particular, we show that the static conformations are best described when the ratio sigma/b=0.6, where sigma is the Lennard-Jones length parameter and b is the monomer bond length. We also find that the decay of the Rouse modes' autocorrelation function is better described with an analytical correction suggested by Ahlrichs and Dunweg. Our FH solver permits us to treat the fluid equation of state and transport parameters as direct simulation parameters. The expected independence of the chain dynamics on various choices of fluid equation of state and bulk viscosity is recovered, while excellent agreement is found for the temperature and shear viscosity dependence of center of mass diffusion between simulation results and predictions of the Zimm model. We find that Zimm model approximations start to fail when the Schmidt number Sc < or approximately 30. Finally, we investigate the importance of fluid fluctuations and show that using the preaveraged approximation for the hydrodynamic tensor leads to around 3% error in the diffusion coefficient for a polymer chain when the fluid discretization size is greater than 50 A.
Sexual dysfunction is a potential side effect of mood stabilizers and anxiolytic drugs: this article presents a critical review of the current literature. Although many studies have been published on ...sexual side effects of psychopharmacological treatment, only a minority relate to mood stabilizers and anxiolytic drugs. Most of these studies are not methodologically robust, few are RCTs and most did not use a validated rating scale to evaluate sexual functioning. In addition, many of the studies on sexual dysfunction associated with mood stabilizers and anxiolytic drugs are limited by other methodological flaws. While there is evidence to suggest that mood stabilizers, with some exceptions, negatively affect sexual functioning, there is still insufficient evidence to draw any clear conclusions about the effects of anxiolytic drugs on sexual function. There is some weak evidence to indicate that switching from enzyme-inducing to non-enzyme-inducing anticonvulsant drugs, could be clinically useful. Some researchers recommend that sexual dysfunction in patients taking antiepileptic drugs should in general be treated according to standard guidelines for the management of sexual dysfunction, since reliable data on special populations is not available. However, specific approaches may be useful, but cannot yet be recommended until further validating research has been conducted. We did not find evidence supporting the use of any specific treatment strategy for sexual dysfunction associated with anxiolytic treatment.
This study was conducted in 2013 using the paper and electronic resources of the library of the Azienda Provinciale per i Servizi Sanitari (APSS) in Trento, Italy (http://atoz.ebsco.com/Titles/2793). The library has access to a wide range of databases including DYNAMED, MEDLINE Full Text, CINAHL Plus Full Text, The Cochrane Library, Micromedex healthcare series, BMJ Clinical Evidence. The full list of available journals can be viewed at http://atoz.ebsco.com/Titles/2793, or at the APSS web site (http://www.apss.tn.it). In completing this review, a literature search was conducted using the key words "anxiolytic drugs", "mood stabilizers", "benzodiazepines", "psychotrophic drugs", "sexual dysfunction", "sexual side effects", "treatment-emergent sexual dysfunction". All resulting listed articles were reviewed.
This review includes studies that investigated the relationship between mood stabilizer and anxiolytic drug treatment and sexual dysfunction. The purpose was to identify possible intervention strategies for sexual dysfunction related to these drugs.
Therapeutic drug monitoring (TDM) aims to optimize pharmacotherapy treatment. Knowledge, availability and use of TDM for psychiatric patients, however, differ between countries. In this survey we ...analysed the practice in Italy of TDM for psychoactive drugs.
A semi-structured questionnaire was sent out to 211 mental health centres (centro di salute mentale) and 10 university hospitals from each region in Italy.
Feedback was obtained from 44 centres. Information collected by the questionnaires indicated that in Italian psychiatry TDM is used for lithium, valproic acid and carbamazepine. With regard to clozapine, TDM was regarded as the blood cell counting which is obligatory when prescribing this drug. TDM was not employed for antidepressant or antipsychotic drug prescribing. Moreover, it appeared that only a few laboratories in Italy offer TDM services for psychiatric patients. Nevertheless, interest was expressed about receiving further information about TDM in psychiatry and participating in training programmes.
This nationwide survey revealed that in Italy, TDM of psychoactive drugs is restricted to only a few drugs. In response to interest expressed, mental health workers should be educated about TDM and more laboratories should be encouraged to establish TDM services for psychotropic drugs.
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