RESUMO
The molecular cross-sectional area (σ) has proved to be an interesting molecular measure not only in the field of adsorption phenomena on solids but also in biochemistry, physiology, or surfactant chemistry. The existing methods to estimate the cross-sectional areas are either not readily applicable or can only be applied to a limited number of compounds. The aim of this work was to describe a method, as general as possible, quick and easy to perform. To that end, the molecular cross-sectional areas were correlated with topological indices. The Emmett-Brunauer formula was used to calculate the reference cross-sectional areas (σEB) of 431 compounds. The correlations of the Wiener (W), hyper-Wiener (WW), Balaban (J), and Randic (χ) indices with σEB were compared for n-alkanes as well as branched and cyclic alkanes. Only the Wiener and hyper-Wiener indices correlated well with σEB, with the data being best fitted by power law regression curves. The lower degeneracy of the hyper-Wiener index did not translate into any significant gain of performance when correlated with σEB. Following the parsimony principle, the less complex Wiener index was thus selected to correlate with the σEB of compounds representing 31 other monofunctional and structural families. The integration of all the compound families into a single curve allowed a quick rough estimation of the cross-sectional areas. The specific reference equations σEB = qWp were determined for the 34 selected families, allowing the fast and reliable calculation of the cross-sectional area of any monofunctional compound.
Assuntos
Compostos Orgânicos , Compostos Orgânicos/química , Alcanos/químicaRESUMO
INTRODUCTION: The purpose of this study was to describe and evaluate the outcomes of an optometrist-led virtual glaucoma clinic (VGC). METHODS: New patients referred to the glaucoma service who were consultant triaged as 'low risk' were assessed virtually by specialist-trained optometrists in the VGC and either discharged or monitored for a period of 3 years. Ten percent of virtual case notes were audited by a glaucoma consultant to verify quality and generate learning objectives. Retrospective case-note review and analysis of all patients seen in the virtual clinic between 2014 and 2016 was undertaken to determine 3-year outcomes. RESULTS: A total of 1710 new patients were seen in the clinic between 1 January 2014 and 31 December 2016. Of these, 1033 (60.4%) patients required no outpatient input in 3 years of follow-up. Additionally, 320 (18.7%) were discharged at the first visit, and the proportion of glaucoma suspect and ocular hypertension patients who converted to glaucoma was 12.1% and 5.8%, respectively. At 3 years, 95 patients had died, 159 were lost to follow-up, 576 were discharged and 371 were diagnosed with glaucoma at baseline or during the 3-year follow-up. The cumulative discharge proportion from the service at the end of 3 years was 82.6%. No patients required emergency eye treatment or sight-impairment registration, and of the 12 referred back to the clinic on discharge, only five required ongoing monitoring. CONCLUSION: This optometrist-led VGC combined two aspects of novel service delivery to reduce the burden of glaucoma monitoring in outpatient departments and consolidate consultant contact to patients requiring more intervention. This model will be of value in units establishing virtual services and looking to expand the role of allied health professionals.
Assuntos
Glaucoma , Hipertensão Ocular , Optometristas , Optometria , Humanos , Pressão Intraocular , Estudos Retrospectivos , Campos Visuais , Glaucoma/diagnóstico , Glaucoma/terapia , Hipertensão Ocular/diagnóstico , Encaminhamento e ConsultaRESUMO
AIMS: Concentration-QT modelling (C-QTc) of first-in-human data has been rapidly adopted as the primary evaluation of QTc interval prolongation risk. Here, we evaluate the performance of C-QTc in early oncology settings (i.e., patients, no placebo or supratherapeutic dose, 3 + 3 designs). METHODS: C-QTc performance was evaluated across three oncology scenarios using a simulation-estimation approach: (scen1) typical dose-escalation testing six dose levels (n = 21); (scen2) small dose-escalation testing two dose levels (n = 9); (scen3) expansion cohorts at one dose level (n = 6-140). True ΔΔQTc effects ranged from 3 ms ("no effect") to 20 ms ("large effect"). Performance was assessed based on the upper limit of the ΔQTc two-sided 90% CI against a threshold of 10 or 20 ms. RESULTS: The performance against the 10 ms threshold was limited based on C-QTc data from typical dose escalation (scen1) and acceptable performance was observed only for relatively large expansions (n ≥ 45; scen3). Performance against the 20 ms threshold was acceptable based on C-QTc data from a typical dose escalation (scen1) or dose expansion cohort n > 10 (scen3). In general, pooling C-QTc data from dose escalation and expansion cohorts substantially improved the performance and reduced the ΔQTc 90% CI width. CONCLUSION: C-QTc performance appeared limited using a 10 ms threshold, but acceptable against a 20 ms threshold. Selection of threshold may be informed by the benefit-risk balance in a specific disease area. Acceptable precision (i.e., confidence intervals) of the estimated ΔQTc, regardless of its magnitude, can be facilitated by pooling data from dose escalation and expansion cohorts.
Assuntos
Eletrocardiografia , Síndrome do QT Longo , Simulação por Computador , Relação Dose-Resposta a Droga , Frequência Cardíaca , Humanos , Síndrome do QT Longo/induzido quimicamente , OncologiaRESUMO
BACKGROUND: For psychiatric service users suffering from severe mental disorders, the social support provided by personal social networks is essential for living a meaningful life within the community. However, the importance of the support received depend on the relations between the providers of social support. Yet this hasn't been addressed in the literature so far for people with severe mental disorders. This article seeks to investigate how characteristics of service users with severe mental disorders, their social contacts, and the pattern of relationships between those contacts influence the distribution and provision of social support to people with severe mental disorders. METHODS: We collected personal network data relating to 380 psychiatric service users from a random sample of health care providers in Belgium. We computed various measures of the structure of those networks and of the position of support persons within those networks. We conducted a multilevel analysis of the importance of the support provided by each support persons. RESULTS: The results show that the more central a support person was in the network of a service user, the more important his or her support was considered to be by the service user. Also, the denser the network in which a support person was embedded, the less important was the support he or she offers, but only for hospitalised service users. CONCLUSION: These finding highlight the collective dimension of social support. We discuss the implications for the organisation of mental health care.
Assuntos
Transtornos Mentais , Masculino , Feminino , Humanos , Análise Multinível , Transtornos Mentais/terapia , Transtornos Mentais/psicologia , Apoio Social , Rede Social , Pessoal de Saúde/psicologiaRESUMO
INTRODUCTION: This article aims to take stock of the ways in which the concept of participation is used in mental health, particularly in the literature relating to patient support. Based on the debates and issues identified, we propose a framework for analyzing participatory practices. METHOD: The methodology is based on a literature review to which a meta-synthesis has been applied. This method of secondary analysis of qualitative research initially made it possible to synthesise and structure knowledge on the subject studied. Secondly, an interpretative analysis has been carried out to identify a proposal for a framework for analyzing practices. RESULTS: The search process, conducted from two databases, returned 28 articles after exclusion for full data extraction and analysis. Through the meta-synthesis of the data, three ideal models of participation in mental health emerged: the linear approach, the conditional approach and the unconditional approach. CONCLUSION: Our results show that the advantage of mobilizing conceptual variations of participation from the point of view of caregivers in health support does not lie in the opposition of concepts. Rather, it rests on the possibility of shedding light on the different forms that this participation takes in the representation of professionals and their evolution in field practice.
Assuntos
Saúde Mental , Participação do Paciente , Humanos , Pesquisa QualitativaRESUMO
PURPOSE: For severely mentally ill (SMI) users, continuity of care requires consistency between the supports provided by the members of their social support network. However, we know little about their network cohesion and its association with continuity of care. We set out to investigate this association and hypothesised that it would depend on the severity of the user's situation and on his/her living arrangements. METHODS: We conducted face-to-face interviews with 380 SMI users recruited in outpatient and inpatient mental health services in three areas in Belgium. Data regarding users' social networks were collected using an ego-network mapping technique and analysed with social network analysis. The cohesion indicators were density (frequency of connections between network members), centralisation (having a small number of central people), and egobetweenness (the user's centrality in his/her own network). Participants' perception of continuity of care was measured by the Alberta Continuity of Services Scale. RESULTS: Results show that cohesion indicators were associated with continuity of care only for users with high-severity problems, regardless of their living arrangements. The numbers of network members, professionals, and services in the network were all negatively associated with continuity of care for all the users. CONCLUSIONS: Satisfactory continuity of care requires fewer professionals or services in a user's network and a dense network for users with the most severe problems. This implies that those providing care must not only be able to increase cohesion within a network, but also to adapt their interventions to support the transition to a different, individualised network structure when severity decreases.
Assuntos
Continuidade da Assistência ao Paciente/estatística & dados numéricos , Transtornos Mentais/psicologia , Transtornos Mentais/terapia , Serviços de Saúde Mental/estatística & dados numéricos , Rede Social , Adulto , Bélgica , Feminino , Humanos , Masculino , Satisfação do Paciente/estatística & dados numéricos , Apoio SocialRESUMO
AIM: In spite of screening procedures in early drug development, uncertainty remains about the propensity of new chemical entities (NCEs) to prolong the QT/QTc interval. The evaluation of proarrhythmic activity using a comprehensive in vitro proarrhythmia assay does not fully account for pharmacokinetic-pharmacodynamic (PKPD) differences in vivo. In the present study, we evaluated the correlation between drug-specific parameters describing QT interval prolongation in dogs and in humans. METHODS: Using estimates of the drug-specific parameter, data on the slopes of the PKPD relationships of nine compounds with varying QT-prolonging effects (cisapride, sotalol, moxifloxacin, carabersat, GSK945237, SB237376 and GSK618334, and two anonymized NCEs) were analysed. Mean slope estimates varied between -0.98 ms µM-1 and 6.1 ms µM-1 in dogs and -10 ms µM-1 and 90 ms µM-1 in humans, indicating a wide range of effects on the QT interval. Linear regression techniques were then applied to characterize the correlation between the parameter estimates across species. RESULTS: For compounds without a mixed ion channel block, a correlation was observed between the drug-specific parameter in dogs and humans (y = -1.709 + 11.6x; R2 = 0.989). These results show that per unit concentration, the drug effect on the QT interval in humans is 11.6-fold larger than in dogs. CONCLUSIONS: Together with information about the expected therapeutic exposure, the evidence of a correlation between the compound-specific parameter in dogs and in humans represents an opportunity for translating preclinical safety data before progression into the clinic. Whereas further investigation is required to establish the generalizability of our findings, this approach can be used with clinical trial simulations to predict the probability of QT prolongation in humans.
Assuntos
Desenho de Fármacos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Síndrome do QT Longo/induzido quimicamente , Modelos Biológicos , Animais , Cães , Eletrocardiografia , Humanos , Modelos Lineares , Síndrome do QT Longo/diagnóstico , Especificidade da EspécieRESUMO
BACKGROUND: Cataract is the leading cause of world blindness. The only available treatment for cataract is surgery. Surgery requires highly-trained individuals with expensive operating facilities. Where these are not available, patients go untreated. A form of treatment that did not involve surgery would be a useful alternative for people with symptomatic cataract who are unable or unwilling to undergo surgery. If an eye drop existed that could reverse or even prevent progression of cataract, then this would be a useful additional treatment option.Cataract tends to result from oxidative stress. The protein, L-carnosine, is known to have an antioxidant effect on the cataractous lens, so biochemically there is sound logic for exploring L-carnosine as an agent to reverse or even prevent progression of cataract. When applied as an eye drop, L-carnosine cannot penetrate the eye. However, when applied to the surface of the eye, N-acetylcarnosine (NAC) penetrates the cornea into the front chamber of the eye (near to where the cataract is), where it is metabolised into L-carnosine. Hence, it is possible that use of NAC eye drops may reverse or even prevent progression of cataract, thereby improving vision and quality of life. OBJECTIVES: To assess the effectiveness of NAC drops to prevent or reverse the progression of cataract. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2016), Embase (January 1980 to June 2016), Allied and Complementary Medicine Database (AMED) (January 1985 to June 2016), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to June 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 28 June 2016. We handsearched the American Society of Cataract and Refractive Surgery (ASCRS) and the European Society of Cataract and Refractive Surgeons (ESCRS) meetings from 2005 until September 2015. SELECTION CRITERIA: We planned to include randomized or quasi-randomised controlled trials where NAC was compared to control in people with age-related cataract. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We identified two potentially eligible studies from Russia and the United States. One study was split into two arms: the first arm ran for six months, with two-monthly follow-up; the second arm ran for two years with six-monthly follow-up. The other study ran for four months with a data collection point at the start and end of the study only. A total of 114 people were enrolled in these studies. The ages ranged from 55 to 80 years.We were unable to obtain sufficient information to reliably determine how both these studies were designed and conducted. We have contacted the author of these studies, but have not yet received a reply. Therefore, these studies are assigned as 'awaiting classification' in the review until sufficient information can be obtained from the authors. AUTHORS' CONCLUSIONS: There is currently no convincing evidence that NAC reverses cataract, nor prevents progression of cataract (defined as a change in cataract appearance either for the better or for the worse). Future studies should be randomized, double-masked, placebo-controlled trials with standardised quality of life outcomes and validated outcome measures in terms of visual acuity, contrast sensitivity and glare, and large enough to detect adverse effects.
Assuntos
Carnosina/análogos & derivados , Catarata/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Carnosina/administração & dosagem , Catarata/etiologia , Progressão da Doença , Humanos , Pessoa de Meia-Idade , Soluções Oftálmicas/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
AIMS: Significant differences between dogs and humans have been observed in the concentration-QTc effect relationship of compounds with known pro-arrhythmic properties. These findings suggest that interspecies differences must be considered when evaluating drug effects. The aim of this study was to evaluate the performance of a model-based approach to assess the risk of QTc prolongation for three investigational compounds (NCE01, NCE02 and NCE03). METHODS: Pharmacokinetic and pharmacodynamic data from experiments in conscious dogs and healthy subjects were included in this analysis. Pharmacokinetic modelling and deconvolution methods were applied to derive drug concentrations at the time of each QT measurement. An integrated pharmacokinetic-pharmacodynamic (PKPD) model was then used to describe QT prolongation. A threshold of ≥10 ms was used to characterize the probability of QTc prolongation. RESULTS: The PKPD relationships of all three compounds were successfully described in both species. A strong effect was observed after administration of NCE01 to dogs and humans, with a slope of 0.0061 and 0.0662 ms nm(-1), respectively, and maximal probability of QTc prolongation ≥10 ms at peak concentration. For NCE02 and NCE03, QTc-shortening and borderline QT effects were observed both in dogs and humans, as described by negative or very shallow slopes (NCE02, -0.00098 and -0.01 ms nm(-1); NCE03, 0.00064 and -0.0002 ms nm(-1)). CONCLUSIONS: Whilst NEC01 shows clear pro-arrhythmic effects, the liability for QT/QTc prolongation for NCE02 and NCE03 can be deemed low at the expected therapeutic exposure. Moreover, our results show the advantages of an integrated PKPD approach as the basis for translating pro-arrhythmic effects from dogs to humans.
Assuntos
Descoberta de Drogas , Drogas em Investigação/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/diagnóstico , Modelos Biológicos , Adulto , Animais , Cães , Método Duplo-Cego , Drogas em Investigação/farmacocinética , Drogas em Investigação/farmacologia , Eletrocardiografia/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa Translacional Biomédica , Adulto JovemRESUMO
AIMS: Given the similarities in QTc response between dogs and humans, dogs are used in pre-clinical cardiovascular safety studies. The objective of our investigation was to characterize the PKPD relationships and identify translational gaps across species following the administration of three compounds known to cause QTc interval prolongation, namely cisapride, d, l-sotalol and moxifloxacin. METHODS: Pharmacokinetic and pharmacodynamic data from experiments in conscious dogs and clinical trials were included in this analysis. First, pharmacokinetic modelling and deconvolution methods were applied to derive drug concentrations at the time of each QT measurement. A Bayesian PKPD model was then used to describe QT prolongation, allowing discrimination of drug-specific effects from other physiological factors known to alter QT interval duration. A threshold of ≥10 ms was used to explore the probability of prolongation after drug administration. RESULTS: A linear relationship was found to best describe the pro-arrhythmic effects of cisapride, d,l-sotalol and moxifloxacin both in dogs and in humans. The drug-specific parameter (slope) in dogs was statistically significantly different from humans. Despite such differences, our results show that the probability of QTc prolongation ≥10 ms in dogs nears 100% for all three compounds at the therapeutic exposure range in humans. CONCLUSIONS: Our findings indicate that the slope of PKPD relationship in conscious dogs may be used as the basis for the prediction of drug-induced QTc prolongation in humans. Furthermore, the risk of QTc prolongation can be expressed in terms of the probability associated with an increase ≥10 ms, allowing direct inferences about the clinical relevance of the pro-arrhythmic potential of a molecule.
Assuntos
Síndrome do QT Longo/induzido quimicamente , Modelos Biológicos , Pesquisa Translacional Biomédica/métodos , Adolescente , Adulto , Animais , Compostos Aza/efeitos adversos , Compostos Aza/farmacocinética , Teorema de Bayes , Cisaprida/efeitos adversos , Cisaprida/farmacocinética , Estudos Cross-Over , Cães , Método Duplo-Cego , Avaliação Pré-Clínica de Medicamentos , Feminino , Fluoroquinolonas , Humanos , Masculino , Pessoa de Meia-Idade , Moxifloxacina , Probabilidade , Quinolinas/efeitos adversos , Quinolinas/farmacocinética , Método Simples-Cego , Sotalol/efeitos adversos , Sotalol/farmacocinética , Especificidade da Espécie , Adulto JovemRESUMO
Fragmentation in mental health and social care delivery should be addressed at the system level. A Social Network Analysis was carried out on relations between services in order to assess Leutz's levels of care integration: linkage, coordination, and full integration. Findings for deprived areas in Brussels and London show that linkage across clusters of services is weak in both networks. However, the integration of care relies on the level of linkage in London, while in Brussels it is more dependent on central services playing brokerage roles. The method offers a useful and complementary basis for evaluating the integration of care.
Assuntos
Comportamento Cooperativo , Serviços de Saúde Mental/organização & administração , Áreas de Pobreza , Rede Social , Serviço Social/organização & administração , Bélgica , Humanos , Londres , Modelos Organizacionais , Inquéritos e Questionários , Populações Vulneráveis/psicologiaRESUMO
Background Blockade of the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a potentially attractive mechanism for lowering inflammatory and lipid risk in patients with atherosclerosis. This study aims to assess the safety, tolerability, and target engagement of MEDI6570, a high-affinity monoclonal blocking antibody to LOX-1. Methods and Results This phase 1, first-in-human, placebo-controlled study (NCT03654313) randomized 88 patients with type 2 diabetes to receive single ascending doses (10, 30, 90, 250, or 500 mg) or multiple ascending doses (90, 150, or 250 mg once monthly for 3 months) of MEDI6570 or placebo. Primary end point was safety; secondary and exploratory end points included pharmacokinetics, immunogenicity, free soluble LOX-1 levels, and change in coronary plaque volume. Mean age was 57.6/58.1 years in the single ascending doses/multiple ascending doses groups, 31.3%/62.5% were female, and mean type 2 diabetes duration was 9.7/8.7 years. Incidence of adverse events was similar among cohorts. MEDI6570 exhibited nonlinear pharmacokinetics, with terminal half-life increasing from 4.6 days (30 mg) to 11.2 days (500 mg), consistent with target-mediated drug disposition. Dose-dependent reductions in mean soluble LOX-1 levels from baseline were observed (>66% at 4 weeks and 71.61-82.96% at 10 weeks in the single ascending doses and multiple ascending doses groups, respectively). After 3 doses, MEDI6570 was associated with nonsignificant regression of noncalcified plaque volume versus placebo (-13.45 mm3 versus -8.25 mm3). Conclusions MEDI6570 was well tolerated and demonstrated dose-dependent soluble LOX-1 suppression and a pharmacokinetic profile consistent with once-monthly dosing. Registration URL: https://clinicaltrials.gov/; Unique identifier: NCT03654313.
Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Lectinas/uso terapêutico , Método Duplo-Cego , Relação Dose-Resposta a DrogaRESUMO
BACKGROUND: Physical exercise therapy is of proven efficacy in the treatment of adults with depression, but corresponding evidence is lacking in depressed adolescent inpatients. The aim of this study was to document the effect of add-on treatment with structured physical exercise in a clinical population of adolescents hospitalized for depression and anxiety in a psychiatric hospital. METHODS: A group of 52 adolescent inpatients was randomly assigned to a physical exercise or control program three to four times per week over a six-week period (20 hours in total). The primary outcome was the Hospital Anxiety Depression Scale (HADS) for evaluation of depression and anxiety symptoms. Secondary outcomes were psychological self-assessments, diagnostic interviews, and physical examinations. RESULTS: Six participants were lost in each group, leaving 20 inpatients each in the intervention and control groups. A linear mixed model with F-test revealed a significant interaction in favor of physical exercise in reducing the mean depression score (HADS-D) by 3.8 points [95% (CI), range 1.8 to 5.7], compared to a mean reduction score of 0.7 [95% (CI), range -0,7 to 2.0] in the control group. No significant interaction was found for anxiety symptoms (HADS-A). LIMITATIONS: The investigation was limited to the six-week hospital window and the small sample size prevented exploring differences in social characteristics. CONCLUSION: Structured physical exercise add-on therapy integrated into the psychiatric hospitalization of adolescents has led to a reduction in their depressive symptoms, demonstrating its effectiveness in the care of adolescent inpatients with depression.
Assuntos
Depressão , Pacientes Internados , Adolescente , Adulto , Ansiedade/psicologia , Transtornos de Ansiedade/terapia , Depressão/psicologia , Exercício Físico , HumanosRESUMO
Mathematical models in oncology aid in the design of drugs and understanding of their mechanisms of action by simulation of drug biodistribution, drug effects, and interaction between tumor and healthy cells. The traditional approach in pharmacometrics is to develop and validate ordinary differential equation models to quantify trends at the population level. In this approach, time-course of biological measurements is modeled continuously, assuming a homogenous population. Another approach, agent-based models, focuses on the behavior and fate of biological entities at the individual level, which subsequently could be summarized to reflect the population level. Heterogeneous cell populations and discrete events are simulated, and spatial distribution can be incorporated. In this tutorial, an agent-based model is presented and compared to an ordinary differential equation model for a tumor efficacy model inhibiting the pERK pathway. We highlight strengths, weaknesses, and opportunities of each approach.
Assuntos
Modelos Teóricos , Neoplasias , Simulação por Computador , Humanos , Modelos Biológicos , Neoplasias/tratamento farmacológico , Distribuição TecidualRESUMO
Objective: We aimed to evaluate the feasibility of an online High-Intensity Interval Training (HIIT) program on clinical psychological symptoms in higher education students in the context of the COVID-19 pandemic lockdown. Materials and Methods: During the lockdown, 30 students aged 18-25 years, who had been screened previously with a cut-off score ≥5 in the Generalized Anxiety Disorder-7 (GAD-7) questionnaire, were randomly assigned to either the 4-week HIIT program with three sessions per week conducted through online videos, or a no-intervention control group. The primary outcome was the feasibility assessment. The secondary outcome was a psychological self-report with the 21-items Depression, Anxiety, and Stress Scale (DASS-21). Assessment and intervention were performed in compliance with social distancing rules. Results: Two participants in the HIIT were lost to follow-up, leaving 13 participants vs. 15 in the control group. We observed high adherence (87%) and complete safety for mental and physical status with the HIIT intervention delivered by online videos. The Mann-Whitney test demonstrated a significant (group × time, P-Value = 0.046) reduction of clinical stress symptoms and a trend (group × time, P-Value = 0.08) toward reduction of clinical depression symptoms, both favoring the HIIT group. No significant (group × time, P-Value = 0.118) interaction was found for anxiety symptoms. Conclusion: The online HIIT program was found to be feasible and safe in a clinical sample of young adults, who were experiencing social and physical restrictions due to COVID-19. HIIT reduced stress and depressive symptoms and thus these preliminary results show promise for broader application among higher education students during the present lockdown necessitated by the global COVID-19 health crisis.
RESUMO
The present data article provides a dataset of psychological scores, additional description of used measures, and descriptive data of participants related to the research article entitled "Impact of physical exercise on depression and anxiety in adolescent inpatients: a randomized controlled trial" (Philippot et al., 2022). This randomized controlled trial aimed at assessing the effect of add-on treatment with structured physical exercise compared to social relaxation activities in a clinical population of adolescents hospitalized for depression and anxiety in a psychiatric hospital. A group of 40 adolescents was randomly assigned to either a physical exercise or a control program three to four times per week over six weeks. The primary outcome was the Hospital Anxiety Depression Scale (HADS) for evaluation of depression and anxiety symptoms. Secondary outcomes were psychological self-assessments (The Zung Self-Assessment Depression Scale (SDS), Beck's abbreviated Depression Inventory (BDI-13), The Child Depression Inventory (CDI), The State-Trait Anxiety Inventory (STAI)), diagnostic interview (Hamilton Depression Rating Scale), and physical examinations (an adapted version of the Astrand-Rhyming Sub-Maximal Effort Test and BMI measures). These questionnaires and tests were filled at baseline and after intervention.
RESUMO
Molecular dynamics is often considered as a numerical experiment. The error bars on the results are therefore mandatory, but sometimes difficult to determine and computationally demanding. As a low-cost approach, we describe the application of the bootstrap (BS) method to the quantification of uncertainties pertaining to the time correlation functions. We chose the autocorrelation functions of velocity and interdiffusion current for a binary ionic mixture as a test bed, and we assessed the merit of the Darken approximation relating both of them. The intrinsic errors related to phase space sampling is investigated comparing the BS method with the reference method of replica. We also study how the BS method can assist in addressing the finite-size effects.
RESUMO
A sequential pharmacokinetic (PK) and pharmacodynamic (PD) model was built with Nonlinear Mixed Effects Modelling based on data from a first-in-human trial of a novel biologic, MEDI7836. MEDI7836 is a human immunoglobulin G1 lambda (IgG1λ-YTE) monoclonal antibody, with an Fc modification to reduce metabolic clearance. MEDI7836 specifically binds to, and functionally neutralizes interleukin-13. Thirty-two healthy male adults were enrolled into a dose-escalation clinical trial. Four active doses were tested (30, 105, 300, and 600 mg) with 6 volunteers enrolled per cohort. Eight volunteers received placebo as control. Following single subcutaneous administration (SC), individual time courses of serum MEDI7836 concentrations, and the resulting serum IL13 modulation in vivo, were quantified. A binding pharmacokinetic-pharmacodynamic (PK-PD) indirect response model was built to characterize the exposure-driven modulation of the target over time by MEDI7836. While the validated bioanalytical assay specification quantified the level of free target (i.e., a free IL13 assay), emerging clinical data suggested dose-dependent increase in systemic IL13 concentration over time, indicative of a total IL13 assay. The target time course was modelled as a linear combination of free target and a percentage of the drug-target complex to fit the clinical data. This novel PK-PD modelling approach integrates independent knowledge about the assay characteristics to successfully elucidate apparently complex observations.
RESUMO
We developed and evaluated a method for making early predictions of best overall response (BOR) and overall survival at 6 months (OS6) in patients with cancer treated with immunotherapy. This method combines machine learning with modeling of longitudinal tumor size data. We applied our method to data from durvalumab-exposed patients with recurrent/metastatic head and neck cancer. A fivefold cross-validation was used for model selection. Independent trial data, with various degrees of data truncation, were used for model validation. Mean classification error rates (90% confidence intervals [CIs]) from cross-validation were 5.99% (90% CI 2.98%-7.50%) for BOR and 19.8% (90% CI 15.8%-39.3%) for OS6. During model validation, the area under the receiver operating characteristic curves was preserved for BOR (0.97, 0.97, and 0.94) and OS6 (0.85, 0.84, and 0.82) at 24, 18, and 12 weeks, respectively. These results suggest our method predicts trial outcomes accurately from early data and could be used to aid drug development.