Cognitive behavior therapy for anxiety disorders in youth: Treatment specificity and mediation effects

The present study investigated the efficacies of Individual CBT (ICBT), Parent Relationship Skill Training (RLST, which targets increasing parental acceptance of youth and increasing autonomy granting) and Parent Reinforcement Skills Training (RLST, which targets increasing parental positive reinforcement and decreasing negative reinforcement). The specific aims were to examine treatment specificity and mediation effects of parenting variables. ICBT was used as a baseline comparison condition. The sample consisted of 253 youth (ages 5-16 years; M = 9.38; SD = 2.42) and their parents. To examine treatment outcome and specificity, the data were analyzed using analysis of variance within a structural equation modeling framework. Mediation was analyzed via structural equation modeling using MPlus. Results indicated that ICBT, RLST, and RFST produced positive treatment outcomes across all indices of change (i.e., clinically significant improvement, anxiety symptom reduction) and across all informants (i.e., youths and parents). RLST was associated with incremental reduction in youth anxiety symptoms beyond ICBT, as per youth report. Treatment specificity effects were found for participants in RFST in terms of parental reinforcement, as per parent report only. Treatment mediation was not found for any of the hypothesized parenting variables (i.e., parental acceptance, parental autonomy granting, parental reinforcement). The results support the use of CBT involving only the youth and the parent and youth together for treating youth anxiety. The findings’ implications are further discussed in terms of the need to conduct further meditational treatment outcome designs in order to continue to advance theory and research in youth anxiety treatment.

Intervención cognitivo-conductual para el control de ansiedad ante la biopsia insicional en pacientes con cáncer de mama

Oncological patients are submitted to invasive exams in order to obtain an accurate diagnosis; these procedures may cause maladaptative reactions (fear, anxiety and pain). Particularly in breast cancer, the most common diagnose technique is the incisional biopsy. Most of the patients are unaware about the procedure and for that reason they may focus their thoughts on possible events such as pain, bleeding, the anesthesia, or the later surgical wound care. Anxiety and pain may provoke physiological, behavioral and emotional complications, and because of this reason, the Behavioral Medicine trained psychologist takes an active role before and after the biopsy. The aim of this study was to evaluate the effect of a cognitive-behavioral program to reduce anxiety in women submitted to incisional biopsy for the first time. There were 10 participants from the Hospital Juárez de México, Oncology service; all of them were treated as external patients. The intervention program focused in psycho-education and passive relaxation training using videos, tape-recorded instructions and pamphlets. Anxiety measures were performed using the IDARE-State inventory, and a visual-analogue scale of anxiety (EEF-A), and the measurement of blood pressure and heart rate). Data were analyzed both intrasubject and intersubject using the Wilcoxon test (p≤0.05). The results show a reduction in anxiety (as in punctuation as in ranges) besides, a reduction in the EEF-A.

La música en el desarrollo de la espiritualidad y la religiosidad. Una aproximación al Cristianismo y al Budismo

La música puede afectar al individuo en todos sus niveles –físico, mental y espiritual–. El presente artículo se centra en el papel que ésta desempeña en el desarrollo de la vida espiritual y trascendental. Para ello, realizaremos un repaso histórico de su evolución estética y social, abordaremos dicho fenómeno a nivel fisiológico y presentaremos sus aplicaciones clínicas y sociales. Seguidamente y a modo de ejemplo de las concepciones de pensamiento occidental y oriental, trataremos la forma en que el cristianismo y el budismo conciben la música dentro de su doctrina. Finalizaremos con algunas reflexiones sobre el tema.

A randomised controlled trial of calcium channel blockade (CCB) with Amlodipine For the treatment oF subcortical ischaEmic vasCular demenTia (AFFECT): study protocol

BACKGROUND: Vascular dementia is the second most common cause of dementia affecting over seven million people worldwide, yet there are no licensed treatments. There is an urgent need for a clinical trial in this patient group. Subcortical ischaemic vascular dementia is the most common variant of vascular dementia. This randomised trial will investigate whether use of calcium channel blockade with amlodipine, a commonly used agent, can provide the first evidence-based pharmacological treatment for subcortical ischaemic vascular dementia.

METHODS/DESIGN: This is a randomised controlled trial of calcium channel blockade with Amlodipine For the treatment oF subcortical ischaEmic vasCular demenTia (AFFECT) to test the hypothesis that treatment with amlodipine can improve outcomes for these patients in a phase IIb, multi-centre, double-blind, placebo-controlled randomised trial. The primary outcome is the change from baseline to 12 months in the Vascular Dementia Assessment Scale cognitive subscale (VADAS-cog). Secondary outcomes include cognitive function, executive function, clinical global impression of change, change in blood pressure, quantitative evaluation of lesion accrual based on magnetic resonance imaging (MRI), health-related quality of life, activities of daily living, non-cognitive dementia symptoms, care-giver burden and care-giver health-related quality of life, cost-effectiveness and institutionalisation. A total of 588 patients will be randomised in a 1:1 ratio to either amlodipine or placebo, recruited from sites across the UK and enrolled in the trial for 104 weeks.

DISCUSSION: There are no treatments licensed for vascular dementia. The most common subtype is subcortical ischaemic vascular dementia (SIVD). This study is designed to investigate whether amlodipine can produce benefits compared to placebo in established SIVD. It is estimated that the numbers of people with VaD and SIVD will increase globally in the future and the results of this study should inform important treatment decisions.

Virtual Clinical Trials in PET Imaging for Improved Diagnosis of and Evaluation of Therapies for Cancer

Thesis (Ph.D.)--University of Washington, 2016-08

Functional Magnetic Resonance Imaging Neurofeedback and Motor training for Parkinson’s Disease: Randomised Trial

Objective: Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback (NF) uses feedback of the patient’s own brain activity to self-regulate brain networks which in turn could lead to a change in behaviour and clinical symptoms. The objective was to determine the effect of neurofeedback and motor training and motor training (MOT) alone on motor and non-motor functions in Parkinson’s disease (PD) in a 10-week small Phase I randomised controlled trial. Methods: 30 patients with PD (Hoehn & Yahr I-III) and no significant comorbidity took part in the trial with random allocation to two groups. Group 1 (NF: 15 patients) received rt-fMRI-NF with motor training. Group 2 (MOT: 15 patients) received motor training alone. The primary outcome measure was the Movement Disorder Society – Unified Parkinson’s Disease Rating Scale-Motor scale (MDS-UPDRS-MS), administered pre- and post-intervention ‘off-medication’. The secondary outcome measures were the ‘on-medication’ MDS-UPDRS, the Parkinson’s disease Questionnaire-39, and quantitative motor assessments after 4 and 10 weeks. Results: Patients in the NF group were able to upregulate activity in the supplementary motor area by using motor imagery. They improved by an average of 4.5 points on the MDS-UPDRS-MS in the ‘off-medication’ state (95% confidence interval: -2.5 to -6.6), whereas the MOT group improved only by 1.9 points (95% confidence interval +3.2 to -6.8). However, the improvement did not differ significantly between the groups. No adverse events were reported in either group. Interpretation: This Phase I study suggests that NF combined with motor training is safe and improves motor symptoms immediately after treatment, but larger trials are needed to explore its superiority over active control conditions. Clinical Trial website : Unique Identifier: NCT01867827 URL: https://clinicaltrials.gov/ct2/show/NCT01867827?term=NCT01867827&rank=1

Clinical Research and Standard of Care — An Unresolved Question?

Ever since the 1996 revision of the Declaration of Helsinki, the World Medical Association has attempted to address ethical and scientific concerns of its diverse stakeholders for Articles 33 (use of placebo) and 34 (posttrial provisions), most recently in 2013. Both are inextricably linked to standard of care, an essential element of any comparative, interventional clinical trial. But has this now 20-year-long ethical debate truly been put to rest? The choice of standard of care in clinical trials remains a complex issue, particularly for comparative trials conducted in emerging countries.

Assessment of the quality of sample labelling for clinical research

Objective: To assess the quality of the labels for clinical trial samples through current regulations, and to analyze its potential correlation with the specific characteristics of each sample. Method: A transversal multicenter study where the clinical trial samples from two third level hospitals were analyzed. The eleven items from Directive 2003/94/EC, as well as the name of the clinical trial and the dose on the label cover, were considered variables for labelling quality. The influence of the characteristics of each sample on labelling quality was also analyzed. Outcome: The study included 503 samples from 220 clinical trials. The mean quality of labelling, understood as the proportion of items from Appendix 13, was of 91.9%. Out of these, 6.6% did not include the name of the sample in the outer face of the label, while in 9.7% the dose was missing. The samples with clinical trial-type samples presented a higher quality (p < 0.049), blinding reduced their quality (p = 0.017), and identification by kit number or by patient increased it (p < 0.01). The promoter was the variable which introduced the highest variability into the analysis. Conclusions: The mean quality of labelling is adequate in the majority of clinical trial samples. The lack of essential information in some samples, such as the clinical trial code and the period of validity, is alarming and might be the potential source for dispensing or administration errors.

Effectiveness of inulin intake on indicators of chronic constipation; a meta-analysis of controlled randomized clinical trials

Background: Constipation is an intestinal dysfunction. Prebiotics, such as inulin, can improve bowel function by positively influencing intestinal biota. Aim: To analyze the scientific evidence for the role of inulin in improving bowel function in patients with chronic constipation. Methods: A meta-analysis of randomized controlled clinical trials was conducted, grounded on a literature search for the period 1995-2013 (descriptors: inulin & constipation) on PubMed, ScieLo and Central Trials Register Cochrane databases. A total of 24 articles were found, 5 of them were selected for this meta-analysis, involving 252 subjects (experimental group: n = 144, control group: n = 108). The quality of the studies was assessed using the Jadad scale. Results: We found a significant overall effect of inulin on stool frequency (DEM = 0.69, 95%CI: 0.04, 1.34), stool consistency (Bristol scale) (DEM = 1.07, 95% CI: 0.70, 1.45), transit time (DEM = -0.57, 95% CI: -0.99, -0.15) and hardness of stool (RR = 0.42, 95% CI: 0.26, 0.70). Pain and bloating do not improve with inulin intake. Conclusions: inulin intake has a positive effect on bowel function.

Première phase d’un programme de recherche sur l’utilisation de vasopresseurs en traumatologie : étude observationnelle et revue systématique

Résumé : Les réanimateurs ont recours à des interventions à la fois médicales et chirurgicales en contexte de choc traumatique. Le rôle des vasopresseurs dans cette prise en charge est controversé. Alors que les lignes directrices américaines considèrent que les vasopresseurs sont contre-indiqués, certains experts européens en encouragent l’utilisation pour diminuer le recours aux liquides intraveineux. Avant d’élaborer un essai clinique, il importe de comprendre la pratique actuelle à laquelle se comparera une intervention expérimentale, ainsi que de connaître le niveau d’incertitude dans la littérature entourant la question de recherche. Le Chapitre 2 de ce travail présente une étude observationnelle effectuée dans un centre régional de traumatologie québécois. Cette étude documente les pratiques de réanimation adoptées par les équipes de traumatologie en 2013, particulièrement le recours aux liquides intraveineux et aux vasopresseurs. Les résultats démontrent que les vasopresseurs ont été utilisés chez plus de 40% des patients, particulièrement les victimes de traumatismes crâniens (RC 10.2, IC 95% 2.7-38.5). De plus, les vasopresseurs ont été administrés dans les phases précoces de la réanimation, soit avant l’administration d’un volume important de liquides. Le Chapitre 3 présente une revue systématique portant sur l’utilisation précoce de vasopresseurs en traumatologie. Les bases de données MEDLINE, EMBASE, CENTRAL et ClinicalTrials.gov ont été interrogées, ainsi que les abrégés présentés dans les conférences majeures en traumatologie depuis 2005. La sélection des études et l’extraction des données ont été effectuées en duplicata. Aucune donnée interprétable n’a pu être extraite des études observationnelles et le seul essai clinique identifié n’avait pas une puissance suffisante (RR de mortalité avec vasopresseurs 1.24, IC 95 % 0.64-2.43). Cette synthèse met en lumière l’incertitude scientifique sur le rôle des vasopresseurs en traumatologie. Les vasopresseurs ont des bénéfices potentiels importants, puisqu’ils permettent entre autres de supporter étroitement l’hémodynamie des patients. En revanche, ils présentent aussi un fort potentiel de dangerosité. Ils sont utilisés fréquemment, malgré l’absence de données sur leurs risques et bénéfices. Ces trouvailles établissent clairement la pertinence clinique et le bien-fondé éthique d’un essai clinique sur le rôle des vasopresseurs dans la prise en charge précoce des victimes de traumatismes.

MRI indices of functional recovery following intracerebral implantation of a human neural stem cell line in a pre-clinical model of ischaemic stroke

Stem cell therapy for ischaemic stroke is an emerging field in light of an increasing number of patients surviving with permanent disability. Several allogenic and autologous cells types are now in clinical trials with preliminary evidence of safety. Some clinical studies have reported functional improvements in some patients. After initial safety evaluation in a Phase 1 study, the conditionally immortalised human neural stem cell line CTX0E03 is currently in a Phase 2 clinical trial (PISCES-II). Previous pre-clinical studies conducted by ReNeuron Ltd, showed evidence of functional recovery in the Bilateral Asymmetry test up to 6 weeks following transplantation into rodent brain, 4 weeks after middle cerebral artery occlusion. Resting-state fMRI is increasingly used to investigate brain function in health and disease, and may also act as a predictor of recovery due to known network changes in the post-stroke recovery period. Resting-state methods have also been applied to non-human primates and rodents which have been found to have analogous resting-state networks to humans. The sensorimotor resting-state network of rodents is impaired following experimental focal ischaemia of the middle cerebral artery territory. However, the effects of stem cell implantation on brain functional networks has not previously been investigated. Prior studies assessed sensorimotor function following sub-cortical implantation of CTX0E03 cells in the rodent post-stroke brain but with no MRI assessments of functional improvements. This thesis presents research on the effect of sub-cortical implantation of CTX0E03 cells on the resting- state sensorimotor network and sensorimotor deficits in the rat following experimental stroke, using protocols based on previous work with this cell line. The work in this thesis identified functional tests of appropriate sensitivity for long-term dysfunction suitable for this laboratory, and investigated non-invasive monitoring of physiological variables required to optimize BOLD signal stability within a high-field MRI scanner. Following experimental stroke, rats demonstrated expected sensorimotor dysfunction and changes in the resting-state sensorimotor network. CTX0E03 cells did not improve post-stroke functional outcome (compared to previous studies) and with no changes in resting-state sensorimotor network activity. However, in control animals, we observed changes in functional networks due to the stereotaxic procedure. This illustrates the sensitivity of resting-state fMRI to stereotaxic procedures. We hypothesise that the damage caused by cell or vehicle implantation may have prevented functional and network recovery which has not been previously identified due to the application of different functional tests. The findings in this thesis represent one of few pre-clinical studies in resting-state fMRI network changes post-stroke and the only to date applying this technique to evaluate functional outcomes following a clinically applicable human neural stem cell treatment for ischaemic stroke. It was found that injury caused by stereotaxic injection should be taken into account when assessing the effectiveness of treatment.

Bayesian analysis of a mastitis control plan to investigate the influence of veterinary prior beliefs on clinical interpretation

The fundamental objective for health research is to determine whether changes should be made to clinical decisions. Decisions made by veterinary surgeons in the light of new research evidence are known to be influenced by their prior beliefs, especially their initial opinions about the plausibility of possible results. In this paper, clinical trial results for a bovine mastitis control plan were evaluated within a Bayesian context, to incorporate a community of prior distributions that represented a spectrum of clinical prior beliefs. The aim was to quantify the effect of veterinary surgeons’ initial viewpoints on the interpretation of the trial results. A Bayesian analysis was conducted using Markov chain Monte Carlo procedures. Stochastic models included a financial cost attributed to a change in clinical mastitis following implementation of the control plan. Prior distributions were incorporated that covered a realistic range of possible clinical viewpoints, including scepticism, enthusiasm and uncertainty. Posterior distributions revealed important differences in the financial gain that clinicians with different starting viewpoints would anticipate from the mastitis control plan, given the actual research results. For example, a severe sceptic would ascribe a probability of 0.50 for a return of <£5 per cow in an average herd that implemented the plan, whereas an enthusiast would ascribe this probability for a return of >£20 per cow. Simulations using increased trial sizes indicated that if the original study was four times as large, an initial sceptic would be more convinced about the efficacy of the control plan but would still anticipate less financial return than an initial enthusiast would anticipate after the original study. In conclusion, it is possible to estimate how clinicians’ prior beliefs influence their interpretation of research evidence. Further research on the extent to which different interpretations of evidence result in changes to clinical practice would be worthwhile.

Risperidone Versus Methylphenidate in Treatment of Preschool Children With Attention-Deficit Hyperactivity Disorder

Background: Attention Deficit Hyperactivity Disorder (ADHD) is a common psychiatric diagnosis among preschool children. Objectives: The aim of this study was to examine the Risperidone treatment compared to Methylphenidate (MPH) in preschool children with ADHD. Patients and Methods: Thirty three outpatient preschool children, aged 3-6 years, diagnosed with ADHD (The diagnosis of ADHD was established by two child and adolescent psychiatrists according to the DSM-IV-TR criteria), participated in a 6-week, double-blind clinical trial with risperidone (0.5-1.5 mg/d) and methylphenidate (5-20 mg/d), in two divided doses. Treatment outcomes were assessed using the Parent ADHD Rating Scale and Conners Rating Scale. Patients were assessed by a child psychiatrist at baseline, 2, 4 and 6 weeks after the medication started. Side effects were also rated by side effects questionnaire. Results: There were no significant differences between the two protocols on the Parent ADHD Rating Scale scores (P > 0.05) and Parent Conners Rating Scale scores (P > 0.05). Both groups showed a significant improvement in ADHD symptoms over the 6 weeks of treatment for parent ADHD Rating Scale (P < 0.001) and Parent Conners Rating Scale (P < 0.001). The most common adverse effects seen with risperidone were daytime drowsiness and anorexia (20%), and with methylphenidate it was anorexia (55%). Conclusions: Results of this study show that risperidone may be effective and well tolerated for ADHD in preschool children, but more researches are needed to clarify the potential benefits and adverse effects in long term use and comorbid conditions.

Efficacy and Safety of Orally Administered Intravenous Midazolam Versus a Commercially Prepared Syrup

Background: Among different categories of sedative agents, benzodiazepines have been prescribed for more than three decades to patients of all ages. The effective and predictable sedative and amnestic effects of benzodiazepines support their use in pediatric patients. Midazolam is one of the most extensively used benzodiazepines in this age group. Oral form of drug is the best accepted route of administration in children. Objectives: The purpose of this study was to compare the efficacy and safety of a commercially midazolam syrup versus orally administered IV midazolam in uncooperative dental patients. Second objective was to determine whether differences concerning sedation success can be explained by child���s behavioral problems and dental fear. Patients and Methods: Eighty eight uncooperative dental patients (Frankl Scales 1,2) aged 3 to 6 years, and ASA I participated in this double blind, parallel randomized, controlled clinical trial. Midazolam was administered in a dose of 0.5 mg/kg for children under the age 5 and 0.2 mg/kg in patients over 5 years of age. Physiologic parameters including heart rate, respiratory rate, oxygen saturation and blood pressure were recorded. Behavior assessment was conducted throughout the course of treatment using Houpt Sedation Rating Scale and at critical moments of treatment (injection and cavity preparation) by North Carolina Scale. Dental fear and behavioral problems were evaluated using Child Fear Schedule Survey-Dental Subscale (CFSS-DS), and Strength and Difficulties Questionnaire (SDQ). Independent t-test, Chi-Square, and Pearson correlation were used for statistical analysis. Results: Acceptable overall sedation ratings were observed in 90% and 86% of syrup and IV/Oral group respectively; Chi-Square P = 0.5. Other domains of Houpt Scale including: sleep, crying and movement were also not significantly different between groups. Physiological parameters remained in normal limits during study without significant difference between groups. Conclusions: “Orally administered IV midazolam” preparation can be used as an alternative for commercially midazolam syrup.

Effectiveness of Acceptance and Commitment Therapy for Depression, Psychological Well-Being and Feeling of Guilt in 7 - 15 Years Old Diabetic Children

Background: Diabetes imposes restrictions on physical, emotional, and social functioning of children and adolescents. Objectives: The aim of this study was to determine effectiveness of acceptance and commitment therapy (ACT) for depression, psychological well-being and feeling of guilt in 7 - 15 years old diabetic children. Patients and Methods: This was a clinical trial with pre-test and post-test design with control group. The study population consisted of 34 participants selected using convenient sampling out of all 7 - 15 years old patients that referred to the Diabetes Association of Tabriz. They were randomly allocated into two equal groups (experimental and control). The experimental group participated in therapy sessions and the control group did not receive any intervention. The research instruments were reynolds child depression scale (RCDS), eysenck feelings of guilt scale and satisfaction with life scale (SWLS). Results: Multivariate covariance analysis (MANCOVA) showed that the treatment was effective on variables of depression, psychological well-being and feeling guilty in 7 - 15 years old diabetic children (P < 0.001). Conclusions: The aforementioned treatment is effective and suggested to be used in other psychosomatic diseases of children.