51 research outputs found
Deterministic constant-temperature dynamics for dissipative quantum systems
A novel method is introduced in order to treat the dissipative dynamics of
quantum systems interacting with a bath of classical degrees of freedom. The
method is based upon an extension of the Nos\`e-Hoover chain (constant
temperature) dynamics to quantum-classical systems. Both adiabatic and
nonadiabatic numerical calculations on the relaxation dynamics of the
spin-boson model show that the quantum-classical Nos\`e-Hoover chain dynamics
represents the thermal noise of the bath in an accurate and simple way.
Numerical comparisons, both with the constant energy calculation and with the
quantum-classical Brownian motion treatment of the bath, show that the
quantum-classical Nos\`e-Hoover Chain dynamics can be used to introduce
dissipation in the evolution of a quantum subsystem even with just one degree
of freedom for the bath. The algorithm can be computationally advantageous in
modeling, within computer simulation, the dynamics of a quantum subsystem
interacting with complex molecular environments.Comment: Revised versio
Molecular-dynamics simulations of glass formation and crystallization in binary liquid metals: Cu-Ag and Cu-Ni
Combinations of QT-prolonging drugs: towards disentangling pharmacokinetic and pharmaco-dynamic effects in their potentially additive nature.
Background: Whether arrhythmia risks will increase if drugs with electrocardiographic (ECG)
QT-prolonging properties are combined is generally supposed but not well studied. Based on
available evidence, the Arizona Center for Education and Research on Therapeutics (AZCERT)
classification defines the risk of QT prolongation for exposure to single drugs. We aimed to
investigate how combining AZCERT drug categories impacts QT duration and how relative drug
exposure affects the extent of pharmacodynamic drug–drug interactions.
Methods: In a cohort of 2558 psychiatric inpatients and outpatients, we modeled whether
AZCERT class and number of coprescribed QT-prolonging drugs correlates with observed
rate-corrected QT duration (QTc) while also considering age, sex, inpatient status, and other
QTc-prolonging risk factors. We concurrently considered administered drug doses and
pharmacokinetic interactions modulating drug clearance to calculate individual weights of
relative exposure with AZCERT drugs. Because QTc duration is concentration-dependent, we
estimated individual drug exposure with these drugs and included this information as weights
in weighted regression analyses.
Results: Drugs attributing a ‘known’ risk for clinical consequences were associated with the
largest QTc prolongations. However, the presence of at least two versus one QTc-prolonging
drug yielded nonsignificant prolongations [exposure-weighted parameter estimates with
95% confidence intervals for ‘known’ risk drugs + 0.93 ms (–8.88;10.75)]. Estimates for
the ‘conditional’ risk class increased upon refinement with relative drug exposure and coadministration of a ‘known’ risk drug as a further risk factor.
Conclusions: These observations indicate that indiscriminate combinations of QTc-prolonging
drugs do not necessarily result in additive QTc prolongation and suggest that QT prolongation
caused by drug combinations strongly depends on the nature of the combination partners and
individual drug exposure. Concurrently, it stresses the value of the AZCERT classification also
for the risk prediction of combination therapies with QT-prolonging drugs
Rationale and design of an independent randomised controlled trial evaluating the effectiveness of aripiprazole or haloperidol in combination with clozapine for treatment-resistant schizophrenia
<p>Abstract</p> <p>Background</p> <p>One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study.</p> <p>Methods/Design</p> <p>The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome.</p> <p>Discussion</p> <p>The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol, provides physicians with a solid evidence base to be directly applied in the routine care of patients with schizophrenia.</p> <p>Trial Registration</p> <p><b>Clincaltrials.gov Identifier</b>: NCT00395915</p
Effectiveness and cost-effectiveness of Self-Help Plus (SH plus ) for preventing mental disorders in refugees and asylum seekers in Europe and Turkey: study protocols for two randomised controlled trials
Introduction: This article describes two randomised controlled trials that will evaluate the effectiveness and cost-effectiveness of Self-Help Plus (SH+), a group self-help intervention developed by the WHO to reduce distress. In these trials SH+ is being tested as a preventative intervention to lower the incidence of mental disorders in asylum seekers and refugees with psychological distress resettled in Europe and Turkey.Methods and analysis: Two prospective, multicentre, randomised, rater-blinded, parallel-group studies will follow participants over a period of 12 months. One trial will be conducted in Europe and one in Turkey. In each trial, 600 asylum seekers and refugees screening positive on the General Health Questionnaire (≥3), but without a formal diagnosis of any mental disorders according to the Mini International Neuropsychiatric Interview, will be randomly allocated to SH+or to enhanced treatment-as-usual. The primary outcome will be a lower incidence of mental disorders at 6 month follow-up. Secondary outcomes will include the evaluation of psychological symptoms, functioning, well-being, treatment acceptability and indicators of intervention cost-effectiveness.Ethics and dissemination: The two trials received ethical clearance from the local Ethics Committees of the participating sites (seven sites), as well as from the WHO Ethics Committee. All participants will provide informed consent before screening and before study inclusion (a two-step procedure). The results of the trials will be disseminated in agreement with a dissemination plan that includes publication(s) in peer-reviewed journals and presentations at relevant national and international conferences and meetings.</p
Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: a protocol for a randomised, independent, pragmatic, multicentre, parallel-group, superiority clinical trial
Psychosocial interventions for post-traumatic stress disorder in refugees and asylum seekers resettled in high-income countries: Systematic review and meta-analysis
Internal funding from the University of Veron
Novel remote electronic medication supply model for opioid-dependent outpatients with polypharmacy––first long-term case study
International dosage differences in fluoxetine clinical trials.
OBJECTIVE: International differences are thought to exist in dosages used by clinicians treating mood disorders. This study examined international dosage differences in antidepressant clinical trials, using a database formed and maintained as a component of a Cochrane review of comparative clinical trials of fluoxetine. METHODS: This systematic review included 132 studies. A detailed set of methodological features and results were abstracted from the original publications and entered into an electronic database. Mean and maximum fluoxetine dosages were compared across countries. To evaluate the dosages of comparison medications, a defined daily dosage (DDD) ratio was calculated as the trial mean dosage divided by the DDD for that drug. RESULTS: Both the maximum and mean dosages for fluoxetine and comparison medications were higher in trials conducted in the US (fluoxetine weighted mean dosage 49.18 mg; 95% CI, 41.30 to 57.05), compared with trials conducted in Europe (fluoxetine weighted mean dosage 29.98 mg; 95% CI, 25.28 to 34.68). Since most clinical trials were conducted in Europe or the US, we could not determine whether different dosages tended to be used in other regions. CONCLUSIONS: International differences in prescriber behaviour may influence, and in turn be influenced by, the conduct of clinical trials. It is difficult to reconcile such differences with the principles of evidence-based medicine
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