The effectiveness of cognitive behaviour therapy for reducing anxiety symptoms following traumatic brain injury: A meta-analysis and systematic review.

BACKGROUND: Anxiety is a common neuropsychological sequela following traumatic brain injury (TBI). Cognitive Behaviour Therapy (CBT) is a recommended, first-line intervention for anxiety disorders in the non-TBI clinical population, however its effectiveness after TBI remains unclear and findings are inconsistent. OBJECTIVE: There are no current meta-analyses exploring the efficacy of CBT as an intervention for anxiety symptoms following TBI, using controlled trials. The aim of the current study, therefore, was to systematically review and synthesize the evidence from controlled trials for the effectiveness of CBT for anxiety, specifically within the TBI population. METHOD: Three electronic databases (Web of Science, PubMed and PsycInfo) were searched and a systematic review of intervention studies utilising CBT and anxiety related outcome measures in a TBI population was performed through searching three electronic databases. Studies were further evaluated for quality of evidence based on Reichow's (2011) quality appraisal tool. Baseline and outcome data were extracted from the 10 controlled trials that met the inclusion criteria, and effect sizes were calculated. RESULTS: A random effects meta-analysis identified a small overall effect size (Cohen's d) of d = -0.26 (95%CI -0.41 to -0.11) of CBT interventions reducing anxiety symptoms following TBI. CONCLUSIONS: This meta-analysis tentatively supports the view that CBT interventions may be effective in reducing anxiety symptoms in some patients following TBI, however the effect sizes are smaller than those reported for non-TBI clinical populations. Clinical implications and limitations of the current meta-analysis are discussed.

Consultation on the feasibility and ethics of specific, probable Controlled Human Infection Model study scenarios in India: A report.

On March 6, 2019, a workshop was held as part of a larger public consultation exercise to evaluate the perceptions of participants from diverse backgrounds of studies involving Controlled Human Infection Models (CHIMs) (1,2) in India, through three specific case scenarios. This workshop was organised by the Health and Humanities Division of the St. John's Research Institute, Bangalore with funding from the Translational Health Science and Technology Institute (TSHTI), Faridabad (www.thsti.res.in), an autonomous institute of the Department of Biotechnology, Government of India This was an on-going effort of the Division to bring public discourse centre stage in the discussion on the use, ethics and regulations related to CHIM studies, and the introduction of such studies in India. Participants included epidemiologists, community/public health experts, microbiologists, infectious disease specialists, basic and translational scientists, ethicists, journalists and lawyers.

Attitudes toward placebo-controlled clinical trials among depressed patients in Japan.

BACKGROUND: Placebo-controlled clinical trials are the standard in the design of clinical studies for the licensing of new drugs. Medical and ethical concerns regarding placebo use still exist in clinical trials of depressed patients. The aim of this study was to investigate the attitudes toward placebo-controlled clinical trials and to assess factors related to the willingness to participate in such trials among depressed patients in Japan. METHODS: A total of 206 depressed patients aged 49.5 ± 15.7 years (mean ± SD) who were admitted to three psychiatric hospitals were recruited for a cross-sectional study from June 2015 to March 2016. After a thorough explanation of the placebo, the study participants completed a brief 14-item questionnaire developed to evaluate patients' attitudes regarding possible participation in placebo-controlled clinical trials. The Quick Inventory of Depressive Symptomatology was also administered to assess depressive symptoms. RESULTS: The results indicated that 47% of the patients would be willing to participate in a placebo-controlled clinical trial. Expectations for the improvement of disease, desire to receive more medical care, encouragement by family or friends, and desire to support the development of new drugs were associated with the willingness to participate in such trials, whereas a belief that additional time would be required for medical examinations and fear of exacerbation of symptoms due to placebo use were associated with non-participation. LIMITATIONS: Patients were asked about possible participation in placebo-controlled clinical trials. CONCLUSIONS: Less than half of the respondents were willing to participate in placebo-controlled clinical trials. Attitudes toward participation in a placebo-controlled clinical trial need to be considered when deciding whether to conduct such a trial.

Placebo Response and Practice Effects in Schizophrenia Cognition Trials.

Importance: Patients' previous experience with performance-based cognitive tests in clinical trials for cognitive impairment associated with schizophrenia can create practice-related improvements. Placebo-controlled trials for cognitive impairment associated with schizophrenia are at risk for these practice effects, which can be difficult to distinguish from placebo effects. Objectives: To conduct a systematic evaluation of the magnitude of practice effects on the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) in cognitive impairment associated with schizophrenia and to examine which demographic, clinical, and cognitive characteristics were associated with improvement in placebo conditions. Design, Setting, and Participants: A blinded review was conducted of data from 813 patients with schizophrenia who were treated with placebo in 12 randomized placebo-controlled clinical trials conducted mostly in outpatient clinics in North America, Europe, Asia, and Latin America from February 22, 2007, to March 1, 2014. A total of 779 patients provided data for the primary outcome measure at baseline and at least 1 follow-up. Seven trials had prebaseline assessments wherein the patients knew that they were not receiving treatment, allowing a comparison of practice and placebo effects in the same patients. Interventions: Placebo compared with various experimental drug treatments. Main Outcomes and Measures: Composite score on the MCCB. Results: Of the 813 patients in the study (260 women and 553 men; mean [SD] age, 41.2 [11.5] years), the mean MCCB composite score at baseline was 22.8 points below the normative mean, and the mean (SEM) total change in the MCCB during receipt of placebo was 1.8 (0.2) T-score points (95% CI, 1.40-2.18), equivalent to a change of 0.18 SD. Practice effects in the 7 studies in which there was a prebaseline assessment were essentially identical to the postbaseline placebo changes. Baseline factors associated with greater improvements in the MCCB during receipt of placebo included more depression/anxiety (F1,438 = 5.41; P = .02), more motivation (F1,272 = 4.63; P = .03), and less improvement from screening to baseline (F1,421 = 59.32; P < .001). Conclusions and Relevance: Placebo effects were minimal and associated with the number of postbaseline assessments and several patient characteristics. Given that the patients performed 2.28 SDs below normative standards on average at baseline, a mean placebo-associated improvement of less than 0.2 SD provides evidence that ceiling effects do not occur in these trials. These minimal changes in the MCCB could not be responsible for effective active treatments failing to separate from placebo.

[Thinking on controlled setting of plarebo acupuncture in clinical trial of acupuncture and moxibustion].

Differences and relations between effects of acupuncture therapy and sham acupuncture are systematically analyzed in this article through the influential factors of acupuncture effect. And it is held that sham acupuncture effect is not exactly equal to placebo effect. The effects of both acupuncture and sham acupuncture are composed by specific effects and non-specific effects, and the differences of non-specific effects between acupunc ture and sham acupuncture can be minimized furthest with blinding and randomized method. Therefore, the difference of acupuncture and sham acupuncture treatment rests with the degree of differences of the specific effects. Only when both of the specific effect of acupuncture and the effect of acupuncture are minimized, can it be applied as the ideal placebo control. Consequently when placebo acupunture are setted up, factors such as the body condition, site of stimulation and stimulation parameters which can influence the specific effect of acupuncture should be taken into consideration to produce the relatively minimum specific effect.

Commentary on Marczinski and colleagues: mixing an energy drink with an alcoholic beverage increases motivation for more alcohol in college students.

BACKGROUND: This commentary discusses the study by Marczinski and colleagues in which they used an alcohol priming procedure to examine the effects of an alcohol/energy drink mixture on the priming effect. METHODS: The significance of the main findings from this study and new avenues of investigation are discussed. RESULTS: Using an alcohol priming paradigm, Marczinski and colleagues report that an alcohol/energy drink combination (AmED) prolongs the desire-to-drink rating compared with alcohol alone. CONCLUSIONS: The results of this laboratory study add to the growing body of literature that the intoxicating effects of AmED are different than the intoxication by alcohol alone.

Placebo, a historical perspective.

Substances and interventions with no specific therapeutic effect have been in use since the dawn of history. The term placebo has first been mentioned in the Scriptures, but it was not until the 19th century that it appeared in a medical context. Although lay people like Voltaire, and physicians such as Sir William Osler, have raised the possibility that much of what physicians did had no specific therapeutic effect, this notion was not shared by the public at large or by the medical profession. It was only by the end of the 18th century that a placebo-controlled trial has been conducted, repudiating the therapeutic effect of mesmerism. The advent, in the late 1940s, of effective treatments, which also had serious adverse effects, made the distinction between placebo and putative, active drug effects more relevant and urgent, and cleared the way for double-blind, randomized, placebo-controlled trials. This in turn triggered an ethical debate on the use of placebo, both in research and in clinical practice. Anthropologists, sociologists, physiologists, and medical researchers are all focusing their efforts on understanding the mechanism, role and modulating factors of placebo.

Shame and guilt/self-blame as predictors of expressed emotion in family members of patients with schizophrenia.

Expressed emotion (EE) is a measure of the family environment reflecting the amount of criticism and emotional over-involvement expressed by a key relative towards a family member with a disorder or impairment. Patients from high EE homes have a poorer illness prognosis than do patients from low EE homes. Despite EE's well-established predictive validity, questions remain regarding why some family members express high levels of EE attitudes while others do not. Based on indirect evidence from previous research, the current study tested whether shame and guilt/self-blame about having a relative with schizophrenia serve as predictors of EE. A sample of 72 family members of patients with schizophrenia completed the Five Minute Speech Sample to measure EE, along with questionnaires assessing self-directed emotions. In line with the hypotheses, higher levels of both shame and guilt/self-blame about having a relative with schizophrenia predicted high EE. Results of the current study elucidate the EE construct and have implications for working with families of patients with schizophrenia.

Predicting psychopharmacological drug effects on actual driving performance (SDLP) from psychometric tests measuring driving-related skills.

RATIONALE: There are various methods to examine driving ability. Comparisons between these methods and their relationship with actual on-road driving is often not determined. OBJECTIVE: The objective of this study was to determine whether laboratory tests measuring driving-related skills could adequately predict on-the-road driving performance during normal traffic. METHODS: Ninety-six healthy volunteers performed a standardized on-the-road driving test. Subjects were instructed to drive with a constant speed and steady lateral position within the right traffic lane. Standard deviation of lateral position (SDLP), i.e., the weaving of the car, was determined. The subjects also performed a psychometric test battery including the DSST, Sternberg memory scanning test, a tracking test, and a divided attention test. Difference scores from placebo for parameters of the psychometric tests and SDLP were computed and correlated with each other. A stepwise linear regression analysis determined the predictive validity of the laboratory test battery to SDLP. RESULTS: Stepwise regression analyses revealed that the combination of five parameters, hard tracking, tracking and reaction time of the divided attention test, and reaction time and percentage of errors of the Sternberg memory scanning test, together had a predictive validity of 33.4%. CONCLUSION: The psychometric tests in this test battery showed insufficient predictive validity to replace the on-the-road driving test during normal traffic.

Placebo effect in child and adolescent psychiatric trials.

Much literature has been written in the field of child psychiatry regarding the placebo as a tool to test drug efficacy in clinical trials, but quite little regarding the placebo effect itself or its clinical use in child psychiatry. In this article, we aim to critically review the literature regarding the placebo effect in children and adolescents with mental disorders, focusing especially on factors influencing the placebo effect and how they may influence the interpretation of clinical trials. The placebo effect seems to be more marked in children than adults, and particularly in children and adolescents with depression, although it is pervasive across ages and is present in non-psychiatric conditions as well. The use of a placebo in clinical trials as a comparator with drugs that have moderate efficacy at most makes it difficult to obtain positive results, and much effort is needed to design very high quality clinical trials that may overcome the limitations of using a placebo. In addition, the placebo effect across ages and clinical conditions must be tested directly (compared with no treatment whenever possible), in order to characterise which placebos work for what and to determine their use in clinical settings.

Hidden administration of drugs.

In placebo-controlled trials, the placebo component of treatments is usually assessed by simulating a therapy through the administration of a dummy treatment (placebo) in order to eliminate the specific effects of the therapy. Recently, a radically different approach to the analysis of placebo responses has been implemented in which placebo responses are assessed without placebo groups. To do this, the placebo (psychological) component is eliminated by conducting hidden (unexpected) administrations of the active treatment. Compelling experimental evidence now shows that when the psychological component is eliminated through the administration of therapies unbeknownst to the patient, the effects of a variety of treatments are significantly reduced. Overall, the experimental data show that the action of different pharmacological agents can be modulated by cognitive and affective factors that can increase or decrease the effects of drugs. This experimental approach is thus a window into the complex interactions between psychology and pharmacodynamics.

African Americans' responses to genetic explanations of lung cancer disparities and their willingness to participate in clinical genetics research.

PURPOSE: To assess whether reactions to genetic explanations for disparities in lung cancer incidence among family members of African American patients with lung cancer are associated with willingness to participate in clinical genetics research. METHODS: Data are reported for 67 self-identified African Americans aged 18 to 55 years who completed a telephone survey assessing reactions to explanations (i.e., genetics, toxin exposure, menthol cigarettes, and race-related stress) for lung cancer disparities. Majority were female (70%), current smokers (57%), and patients' biological relatives (70%). RESULTS: Family members rated the four explanations similarly, each as believable, fair, and not too worrisome. Participants also indicated a high level of willingness to participate in genetics research (M = 4.1 +/- 1.0; scale: 1-5). Endorsements of genetics explanations for disparities as believable and fair, and toxin exposure as believable were associated significantly with willingness to participate in genetics research. CONCLUSION: These results suggest that strategies to encourage African Americans' participation in genetics research would do well to inform potential participants of how their involvement might be used to better understand important environmental factors that affect health disparities.

Ensaios clínicos com vacinas anti-HIV/AIDS: a rotina de incorporação de uma prática científica / Clinical trials in anti-HIV/AIDS vaccine: the routine of incorporating a scientific practice

O estudo acompanha a rotina de um ensaio clínico de vacinas experimentais anti-HIV/AIDS desenvolvido no Projeto Praça Onze, da UFRJ, em colaboração com a rede mundial de pesquisas de vacinas anti-HIV/AIDS, HVTN (HIV Vaccine Trials Network) e apoio financeiro dos NIH (National Institutes of Health), dos EUA. Focaliza os processos de recrutamento, seleção e seguimento dos voluntários, articulando os aspectos mais gerais àsparticularidades e demandas locais deste estudo realizado no Rio de Janeiro, Brasil. Do ponto de vista teórico-conceitual utiliza recursos oriundos das ciências sociais -história, sociologia da ciência e da corrente interacionista da sociologia. O estudo mostra que, como todo ensaio clínico, o experimento do Projeto Praça Onze é uma atividade coletiva,sustentada sobre múltiplos atores e instâncias, com diversas racionalidades, o que gera uma permanente tensão. Estuda a tensão que se coloca, principalmente entre a expectativa dosprofissionais envolvidos (aconselhadores, recrutadores, médicos, enfermeiros, farmacêuticos, gerentes e coordenadores de estudos) e a experiência vivenciada pelos voluntários, assim como as possíveis negociações propostas durante o desenvolvimento do protocolo, a partir do contexto sociopolítico onde o mesmo está inserido. Os profissionais, apesar de suas especificidades, articulam-se para incorporar do universo dos colegas suas linguagens e seus modos de agir, num processo de hibridização dos conhecimentos e práticas. Os voluntários do ensaio, por sua vez, submetem-se, por um lado a uma rotina de disciplina e compromisso, queimplica na entrega de seu corpo à medicina, implícita nesse papel. Por outro, apropriam-se da lógica do ensaio clínico para, em sua ótica, transformar-se em um co-adjuvante no descobrimento de uma nova biotecnologia, que neste caso, se coloca como uma questão de vida ou morte, para ele e para uma ampla comunidade de infectados pelo HIV...

Treatment-emergent adverse events from selective serotonin reuptake inhibitors by age group: children versus adolescents.

OBJECTIVE: The aim of this study was to report the frequency of common treatment-emergent adverse events (AEs) from selective serotonin reuptake inhibitors (SSRIs) in children, adolescents, and adults. METHOD: AE data were obtained from all published double-blind, placebo-controlled SSRI studies of children and adolescents that separated AE findings by age group. The AE findings were pooled for purposes of age-group comparisons. Double-blind, placebo-controlled SSRI studies of adolescents (n = 2) and of adults identified in systematically identified trials (n = 22) were assessed to compare patterns and rates across the age span. Other reports, primarily from the published SSRI literature, were added to clarify the findings presented. RESULTS: Activation and vomiting SSRI AEs were 2- to 3-fold more prevalent in children than in adolescents, and their rate was lowest in adults. Somnolence as a SSRI AE was uncommon in children; its rate increased with advancing age. Insomnia and nausea were common SSRI AEs across the age span. Activation AEs were a frequent reason for discontinuation from SSRI clinical trials in preadolescents, whereas somnolence, nausea, and insomnia AEs were the most common reasons for trial discontinuations in adults. CONCLUSIONS: Children are particularly vulnerable to specific AEs from certain medications, such as SSRIs. It is likely that the level of children's biological immaturity explains part of this phenomenon.

Attitudes of patients with schizophrenia toward placebo-controlled clinical trials.

BACKGROUND: Despite the fact that the efficacy of antipsychotic treatment in patients with schizophrenia has been demonstrated in numerous double-blind studies, placebo-controlled studies are still commonly performed. Although much is known about the opinions of professionals concerning this issue, so far nothing is known about the opinions of patients who are most affected by the realization of placebo-controlled clinical trials. METHOD: In a cross-sectional study from June 2000 to January 2001, 100 inpatients and outpatients with ICD-10 schizophrenia or schizophreniform disorder were investigated by using a questionnaire specifically developed to survey patients' attitudes concerning possible participation in placebo-controlled clinical trials. Psychopathology and side effects were physician-rated. RESULTS: 56% of patients would not be willing to participate in a placebo-controlled clinical trial. On the other hand, only about 16% of the patients are against clinical trials in principle. Gender, treatment, severity of psychopathology (Positive and Negative Syndrome Scale), adverse events (UKU Side Effect Rating Scale), and attitude toward medication (Drug Attitude Inventory) had no statistically significant influence on the decision. Most of the patients (76%) stated that they would not lose trust in their physician if asked to participate in a placebo-controlled clinical trial. CONCLUSION: The opinions and fears of patients who are most affected by the debate need to be considered when deciding whether a placebo-controlled clinical trial is necessary.