Search

Background: In April 2020, two independent clinical trials to assess SARS-CoV-2 prophylaxis strategies among health care workers were initiated at our hospital: MeCOVID (melatonin vs placebo) and EPICOS (tenofovir disoproxil/emtricitabine vs hydroxychloroquine vs combination therapy vs placebo)., Objective: This study aimed to evaluate the reasons why health care workers chose to participate in the MeCOVID and EPICOS trials, as well as why they chose one over the other., Methods: Both trials were offered to health care workers through an internal news bulletin. After an initial screening visit, all subjects were asked to respond to a web-based survey., Results: In the first month, 206 health care workers were screened and 160 were randomized. The survey participation was high at 73.3%. Health care workers cited "to contribute to scientific knowledge" (n=80, 53.0%), followed by "to avoid SARS-CoV-2 infection" (n=33, 21.9%) and "the interest to be tested for SARS-CoV-2" (n=28, 18.5%), as their primary reasons to participate in the trials. We observed significant differences in the expected personal benefits across physicians and nurses (P=.01). The vast majority of volunteers (n=202, 98.0%) selected the MeCOVID trial, their primary reason being their concern regarding adverse reactions to treatments in the EPICOS trial (n=102, 69.4%)., Conclusions: Health care workers' reasons to participate in prophylaxis trials in an acute pandemic context appear to be driven largely by their desire to contribute to science and to gain health benefits. Safety outweighed efficacy when choosing between the two clinical trials., (©Alberto M Borobia, Irene García-García, Lucía Díaz-García, Amelia Rodríguez-Mariblanca, Lucía Martínez de Soto, Jaime Monserrat Villatoro, Enrique Seco Meseguer, Juan J González, Jesús Frías Iniesta, Elena Ramírez García, Jose Ramón Arribas, Antonio J Carcas-Sansuán. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 25.02.2021.)

The COVID-19 pandemic has magnified the importance of clinical trials for finding a safe and effective vaccine to protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19. Although communication about vaccines and vaccine hesitancy were challenges long before COVID-19, the twin facts of a pandemic and an "infodemic" of health information, misinformation, and disinformation have raised new challenges for vaccine-related communication and decision-making. The goal of this commentary is to highlight strategies to improve communication and decision-making for adults considering participation in COVID-19 vaccine clinical trials. First, I present a general conceptual model for clinical trial participation that can be applied to various vaccine and other clinical trial contexts. Next, I introduce the ASK (Assume, Seek, Know) approach for enhancing clinical trial participation: (1) assume that all patients will want to know their options, (2) seek the counsel of stakeholders, and (3) know your numbers. The ideas presented in this commentary are intended to enhance vaccine-specific clinical trial communication, decision-making, and literacy, while dually offering strategies and resources that may help reduce vaccine hesitancy and increase vaccine uptake over time.

Antenatal progesterone prevents preterm birth (PTB) in women with a short cervix or prior PTB in daily vaginal or weekly injectable formulations, respectively. Neither has been tested for the indication of maternal HIV, which is associated with an elevated risk of PTB. The Vaginal Progesterone (VP) Trial was a pilot feasibility study of VP to prevent HIV-related PTB in Lusaka, Zambia. Using mixed methods, we concurrently evaluated the acceptability of the trial and the study product among participants. Over a 1-year period, we enrolled 140 pregnant women living with HIV into a double-masked, placebo-controlled, randomized trial of daily self-administered VP or placebo. We administered an endline questionnaire to all participants and conducted in-depth interviews with 30 participants to assess barriers and facilitators to uptake and retention in the trial and to study product adherence. All interviews were audiotaped, transcribed, translated into English as needed, and independently coded by two analysts to capture emerging themes. Of 131 participants who completed the questionnaire, 128 (98%) reported that nothing was difficult when asked the hardest part about using the study product. When given a hypothetical choice between vaginal and injectable progesterone, 97 (74%) chose vaginal, 31 (24%) injectable, and 3 (2%) stated no preference. Most interviewees reported no difficulties with using the study product; others cited minor side effects and surmountable challenges. Strategies that supported adherence included setting alarms, aligning dosing with antiretrovirals, receiving encouragement from friends and family, sensing a benefit to their unborn baby, and positive feedback from study staff. Participants who reported preference of a vaginal medication over injectable described familiarity with the vaginal product, a fear of needles and resulting pain, and inconvenience of a weekly clinic visit. Those who would prefer weekly injections cited fewer doses to remember. Perceived barriers to study participation included mistrust about the motivations behind research, suspicion of Satanism, and futility or possible harm from a placebo. We report key influences on acceptability of a randomized trial of VP to prevent PTB among HIV-infected women in Zambia, which should inform methods to promote uptake, adherence, and retention in a full-scale trial., Competing Interests: The authors have declared that no competing interests exist.

Objective: To explore the delivery of home and hospital management at diagnosis of type 1 diabetes in childhood and any impact this had on health professionals delivering care., Methods: This qualitative study was undertaken as part of the Delivering Early Care in Diabetes Evaluation randomized controlled trial where participants were individually randomized to receive initiation of management at diagnosis, to home or hospital. Semi-structured telephone interviews were planned with a purposive sample of health professionals involved with the delivery of home and hospital management, to include consultants, diabetes and research nurses, and dieticians from the eight UK centres taking part. The interview schedule focused on their experiences of delivering the two models of care; preferences, impact, and future plans. Data were subject to thematic analysis., Results: Twenty-two health professionals participated, represented by consultants, diabetes and research nurses, and dieticians. Overall, nurses preferred home management and perceived it to be beneficial in terms of facilitating a unique opportunity to understand family life and provide education to extended family members. Nurses described a special bond and lasting relationship that they developed with the home managed children and families. Consultants expressed concern that it jeopardized their relationship with families. Dieticians reported being unable to deliver short bursts of education to families in the home managed arm. All health professionals were equally divided over which was logistically easier to deliver., Conclusions: A hybrid approach, of a brief stay in hospital and early home management, offers a pragmatic solution to the advantages and challenges presented by both systems., (© 2020 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd.)

Studies show that conservative management in acute uncomplicated appendicitis (AUA) is an alternative to surgery. This study aims to determine factors affecting parental preference in management of AUA and their decision for research participation. We conducted surveys on parents whose children were admitted with suspicion of appendicitis but later confirmed not to have appendicitis. Information on appendicectomy versus conservative treatment with antibiotics was provided using a fixed script and standard information leaflet. Questionnaires covered factors influencing decisions, opinions regarding research, treatment preference and demographic data. We excluded parents not fluent in English. Of 113 respondents, 71(62.8%) chose antibiotics, 39(34.5%) chose appendicectomy, and 3(2.7%) had no preference. Reasons given for choosing antibiotics were fear of surgical risks and preferring less invasive treatment. Those choosing appendicectomy expressed preference for definitive treatment and fear of recurrence. Majority were against randomisation (n = 89, 78.8%) and blinding (n = 90, 79.7%). Over half found difficulty involving their child in research (n = 65, 57.5%). Most thought that research is important (66.4%) and beneficial to others (59.3%). Parents who perceived their child as healthy found research riskier (p = 0.039). Educated parents were more likely to find research beneficial to others (p = 0.012) but less accepting of randomisation (p = 0.001).Conclusion: More parents appear to prefer conservative treatment for acute uncomplicated appendicitis. Researchers must consider parental concerns regarding randomisation and blinding.What is Known:• Conservative management of acute uncomplicated appendicitis in paediatric patients is safe and effective, sparing the child the need for an operation; however, neither conservative nor surgical management is proven to be superior.• Randomised controlled trials provide the highest level of evidence, but it is challenging to recruit paediatric patients as participants in such clinical trials.What is New:• More parents prefer conservative management of uncomplicated appendicitis over surgical management for their children due to fear of surgical risks and complications• Randomisation in trial design is significantly associated with a parent's decision to reject their child's participation in a clinical trial.

Objectives: Given the disparity that exists in enrollment of minorities to oncology clinical trials, the objective of our study was to assess whether race is associated with willingness to participate in gynecologic oncology clinical trials in a rural Southern academic medicine setting. Our secondary aim was to determine whether willingness to participate is impacted by an educational intervention., Methods: A single institution prospective survey study was performed at an academic medical center. Women presenting to the gynecologic oncology clinic with a current or prior diagnosis of gynecologic malignancy were approached to participate. The validated Attitudes to Randomized Trials Questionnaire (ARTQ) assessed willingness to participate in clinical trials. Relevant demographic and clinical data were abstracted. Characteristics were compared between those willing and unwilling to participate in clinical trials with a chi-square test for categorical variables and Wilcoxon rank sum tests for continuous data., Results: We enrolled 156 participants (50% White, 50% non-White) from May 2017 to January 2018. The minority group included 35% non-Hispanic Black, 9% Hispanic, 4% Asian, and 2% other. Median age was 63 years with endometrial cancer being the most common diagnosis (48%). On initial screen, only 35% were willing to participate in a clinical trial. Willingness to participate did not differ between race, age, marital status, education level, cancer type, stage, or mode of treatment. Rates improved to 82% after being provided additional educational information. Following education, White women and those with more education were significantly more willing to participate in clinical trials than their minority and less educated counterparts., Conclusions: Willingness to participate improved among all sub-categories following an educational intervention. The increase in willingness was less robust among racial and ethnic minorities, suggesting that different tools are needed for recruitment of minorities to gynecologic oncology clinical trials., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to report., (Copyright © 2020. Published by Elsevier Inc.)

Background The number of global clinical trials is increasing. Recruitment rate in clinical trials is a challenging task that affects sample size, power of the study, and adequate representation of the targeted population. An understanding of the worries and reasons why patients may refrain from participation in trials may lead to improved enrollment rates. Objectives To assess the rate of patients who are willing to participate in clinical trials, and aspects that might have an impact on the patients' willingness to participate. Setting Government tertiary hospital in Jordan. Methods This is a cross-sectional study. Patients were interviewed by pharmacists in different clinics in a tertiary hospital and information was collected using a data collection sheet. Main outcome measure Factors that might predict the inclination of a patient to participate in clinical trials, and the rate of willingness to participation in randomized controlled trials in cancer patients compared to non-cancer patients. Results A total of 1193 participants were enrolled in the study, one hundred and thirty-five participants (11.3%) had cancer and 80% of the participants had at least one chronic medical condition. Majority of patients (n = 882, 73.9%) believed that trials were safe and 1106 (92.7%) patients thought they were important. Age, education level, income, having cancer or any chronic medical condition, and degree of control of chronic diseases were statistically significant predictors of the willingness of patients to participate in trials. Patients with cancer had a higher rate of acceptance to participation in randomized controlled trials compared to non-cancer patients, 80.0% versus 62.4%, p value < 0.001. Conclusion In general, almost two-thirds of patients were willing to participate in clinical trials, with a higher rate in cancer patients. Factors such as education level, income, and extent of control of medical conditions that might refrain patients from enrollment in trials will lower recruitment rate and must be addressed and taken into consideration before launching clinical trials.

Background: Cognitive Training (CT) has demonstrated some benefits to cognitive and psychosocial function in Mild Cognitive Impairment (MCI) and early dementia, but the certainty related to those findings remains unclear. Therefore, understanding the mechanisms by which CT improves cognitive functioning may help to understand the relationships between CT and cognitive function. The purpose of this review was to identify the evidence for neuroimaging outcomes in studies of CT in MCI and early Alzheimer's Disease (AD)., Methods: Medline, Embase, Web of Science, PsycINFO, CINAHL, and The Cochrane Library were searched with a predefined search strategy, which yielded 1778 articles. Studies were suitable for inclusion where a CT program was used in patients with MCI or AD, with a structural or functional Magnetic Resonance Imaging (MRI) outcome. Studies were assessed for quality using the Downs and Black criteria., Results: A total of 19 studies met the inclusion criteria. Quality of the included studies was variable and there was significant heterogeneity for studies included in this review. Task activation was generally increased post-training, but functional connectivity was both increased and decreased after training. Results varied by diagnosis, type of CT program, and brain networks examined. No effects were seen on hippocampal volumes post-training, but cortical thickening and increased grey matter volumes were demonstrated., Conclusions: CT resulted in variable functional and structural changes in dementia, and conclusions are limited by heterogeneity and study quality. Larger, more robust studies are required to correlate these findings with clinical benefits from CT., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: There are limited data comparing the consistency of angina reporting by patients and clinicians., Methods: We performed a retrospective analysis of data from the randomised Stent or Surgery (SoS) trial. The trial required reporting of angina using the Canadian Cardiovascular Society (CCS) classification by both patients and clinicians at baseline and twelve months. We compared paired observations to describe the magnitude and direction of differences in clinician and patient reporting. The difference in CCS grade was expressed as the clinician minus patient value. We also examined the proportion of trial subjects reported as being free from angina (CCS = 0) in clinician and patient reporting., Results: Paired CCS data was available for 912 and 887 cases at baseline and 12 months respectively. At baseline, clinicians reported freedom from angina in a single case (1/912 = 0.1%) compared to 70/912 (7.7%) patients (Delta 7.6% 95% CI 5.8 to 9.3, P ≤0.001). At 12 months, the position was reversed, with clinicians reporting 639/887 (72%) angina free compared to 449/887 (50.6%) for patients (Delta -21.4 95% CI -17.1 to -25.8 P ≤ 0.001). For the reported CCS grade at follow-up, the weighted linear kappa for overall agreement was 0.312. Discordant reporting involved the clinician suggesting less angina rather than more (36% v 8% of cases)., Conclusions: These findings have implications for our perception of previous research which has, in the main, focussed on clinician reporting. This emphasises the importance of patient reporting and a need to better understand reasons for discordance., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In this paper, I suggest that placebo effects, as we know them today, should be understood as experimental phenomena, low-level regularities whose causal structure is grasped through particular experimental designs with little theoretical guidance. Focusing on placebo interventions with needles for pain reduction -one of the few placebo regularities that seems to arise in meta-analytical studies- I discuss the extent to which it is possible to decompose the different factors at play through more fine-grained randomized clinical trials. My sceptical argument is twofold. On the one hand, I argue that experiments alone are not enough to standardize interventions, and that it is necessary to include theories. On the other hand, I argue that the social interactions that seem to be part of placebo effects are difficult, if not impossible, to blind. Therefore, the measurement biases arising from the participants' reactivity to the experimental setup cannot be controlled for. Further decomposition of placebo effects requires a theoretical account of the existing experimental regularities that may guide further tests., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Some patients with major depression continue to demonstrate deficits in health-related quality of life (HRQL) following remission. No data exist, however, regarding HRQL in remitted psychotic depression. In this study, we aimed to characterize HRQL in patients with psychotic depression receiving controlled pharmacotherapy., Methods: This is a secondary analysis of a randomized controlled trial studying continuation pharmacotherapy of psychotic depression. We compared participants' HRQL (measured using the SF-36) between baseline and remission and to population norms. We also compared SF-36 scores stratified by age and gender and examined the correlation between SF-36 scores and medical burden, depression score and neuropsychological performance in remission., Results: SF-36 scores were significantly lower than population norms at baseline, but improved following remission to the level of population norms. Neither SF-36 scores nor magnitude of SF-36 improvement differed substantially between genders or between younger and older participants. In remission, depression scores were correlated with most SF-36 scales and medical burden was correlated with SF-36 scales measuring physical symptoms. Neuropsychological measures were generally not correlated with SF-36 scores., Limitations: This study was a secondary analysis not powered specifically to measure HRQL as an outcome variable and the SF-36 was the only HRQL measure used., Conclusions: Participants with remitted psychotic depression demonstrated levels of HRQL comparable to population norms, despite marked impairment in HRQL when acutely ill. This finding suggests that, when treated in a rigorous manner, many patients with this severe illness improve significantly from a clinical and HRQL perspective., (Copyright © 2019. Published by Elsevier B.V.)

Background: Interventions that enable people to remain in their own home as they age are of interest to stakeholders, yet detailed information on effective interventions is scarce. Our objective was to systematically search and synthesise evidence for the effectiveness of community-based, aged care interventions in delaying or avoiding admission to residential aged care., Method: Nine databases were searched from January 2000 to February 2018 for English publications. Reference lists of relevant publications were searched. The databases yielded 55,221 citations and 50 citations were gleaned from other sources. Where there was sufficient homogeneity of study design, population, intervention and measures, meta-analyses were performed. Studies were grouped by the type of intervention: complex multifactorial interventions, minimal/single focus interventions, restorative programs, or by the target population (e.g. participants with dementia)., Results: Data from 31 randomised controlled trials (32 articles) that met our inclusion criteria were extracted and analysed. Compared to controls, complex multifactorial interventions in community aged care significantly improved older adults' ability to remain living at home (risk difference - 0.02; 95% CI -0.03, - 0.00; p = 0.04). Commonalities in the 13 studies with complex interventions were the use of comprehensive assessment, regular reviews, case management, care planning, referrals to additional services, individualised interventions, frequent client contact if required, and liaison with General Practitioners. Complex interventions did not have a significantly different effect on mortality. Single focus interventions did not show a significant effect in reducing residential aged care admissions (risk difference 0, 95% CI -0.01, 0.01; p = 0.71), nor for mortality or quality of life. Subgroup analysis of complex interventions for people with dementia showed significant risk reduction for residential aged care admissions (RD -0.05; 95% CI -0.09, -0.01; p = 0.02). Compared to controls, only interventions targeting participants with dementia had a significant effect on improving quality of life (SMD 3.38, 95% CI 3.02, 3.74; p < 0.000001)., Conclusions: Where the goal is to avoid residential aged care admission for people with or without dementia, there is evidence for multifactorial, individualised community programs. The evidence suggests these interventions do not result in greater mortality and hence are safe. Minimal, single focus interventions will not achieve the targeted outcomes., Trial Registration: PROSPERO Registration CRD42016050086 .

Rural-residing cancer patients often do not participate in clinical trials. Many patients misunderstand cancer clinical trials and their rights as participant. The purpose of this study is to modify a previously developed cancer clinical trials decision aid (DA), incorporating the unique needs of rural populations, and test its impact on knowledge and decision outcomes. The study was conducted in two phases. Phase I recruited 15 rural-residing cancer survivors in a qualitative usability study. Participants navigated the original DA and provided feedback regarding usability and implementation in rural settings. Phase II recruited 31 newly diagnosed rural-residing cancer patients. Patients completed a survey before and after using the revised DA, R-CHOICES. Primary outcomes included decisional conflict, decision self-efficacy, knowledge, communication self-efficacy, and attitudes towards and willingness to consider joining a trial. In phase I, the DA was viewed positively by rural-residing cancer survivors. Participants provided important feedback about factors rural-residing patients consider when thinking about trial participation. In phase II, after using R-CHOICES, participants had higher certainty about their choice (mean post-test = 3.10 vs. pre-test = 2.67; P = 0.025) and higher trial knowledge (mean percentage correct at post-test = 73.58 vs. pre-test = 57.77; P < 0.001). There was no significant change in decision self-efficacy, communication self-efficacy, and attitudes towards or willingness to join trials. The R-CHOICES improved rural-residing patients' knowledge of cancer clinical trials and reduced conflict about making a trial decision. More research is needed on ways to further support decisions about trial participation among this population.

IntroductionDespite consistently high discontinuation rates due to withdrawal of consent (WOC) and insufficient therapeutic effect (ITE) in schizophrenia trials, insight into the underlying factors contributing to poor satisfaction with treatment and dropout is limited. A better understanding of these factors could help to improve trial design and completion rates., Methods: Using data from 1,136 trial participants with schizophrenia or schizoaffective disorder, we explored associations between predictor variables with (1) dropout due to WOC and ITE and (2) satisfaction with treatment among patients and investigators by means of hierarchic multiple regression analyses., Results: ITE was associated with poor clinical improvement, poor investigator satisfaction with treatment, and poor patient insight into their own disease, whereas WOC only showed a meaningful association with poor patient satisfaction with treatment. Investigator satisfaction with treatment appeared most strongly associated with Positive and Negative Syndrome Scale (PANSS) positive factor endpoint scores, whereas patient satisfaction with treatment was best predicted by the endpoint score on the PANSS emotional distress factor. The occurrence of severe side effects showed no meaningful association to satisfaction with treatment among investigators and patients, and neither did a patient's experienced psychopathology, nor their self-rating of functional impairment., Conclusions: Whereas trial discontinuation due to ITE is associated with poor treatment effectiveness, a patient's decision to withdraw from an antipsychotic trial remains unpredictable and may occur even when the investigator observes a global clinical improvement and is satisfied with the treatment.

&nbsp; AIM OF THE STUDY: The internal validity of double blinding in randomised placebo-controlled trials (RCTs) has become a target of criticism. The goal of this study was to investigate (a) how accurately the patients and their treating physicians were able to guess their assigned treatment, and (b) predictors for an accurate guess., Methods: Data on treatment estimation from patients (n = 382) and their physicians (n = 358 guesses) in an RCT investigating the role of adjunct prednisone for community-acquired pneumonia in a tertiary care setting were analysed. At discharge, patients and their physicians had to guess whether they had been assigned to the prednisone or to the placebo group. The alternative possibility was &ldquo;uncertain&rdquo;. Percentages and confidence intervals (CIs) were calculated for the proportion of patients guessing correctly. Chance finding was defined as having 50% or less correct guesses. To test for predictors for prednisone treatment guess, a mixed effects logistic regression model was performed., Results: In the prednisone group, 28.9% (55/190; 95% CI 22.6&ndash;36.0%) of the patients made a correct guess and the majority (61.6%, 117/190) was uncertain. In the placebo group, 13.0% (25/192; 95% CI 8.8&ndash;18.8%) guessed correctly, with the majority being uncertain (69.8%, 134/192). Physicians guessed correctly in 48.3% (87/180, 95% CI 40.8&ndash;55.9%) of cases in the prednisone group and in 66.3% (118/178, 95% CI 58.8&ndash;73.2%) of cases in the placebo group, which was above chance for the placebo group. The physicians were uncertain in 21.7% (39/180) of cases in the prednisone group, and in 15.2% (27/178) of cases in the placebo group. Significant predictors for guessing prednisone were the occurrence of hyperglycaemia (odds ratio [OR] 3.77, 95% CI 2.39&ndash;5.95; p&lt;0.001) and a shorter time to clinical stability (OR 0.95, 95% CI 0.91&ndash;0.99; p = 0.02)., Conclusions: We confirmed that patient blinding was achieved in this study. Physicians made correct guesses more often than patients. Treatment estimation by both patients and physicians was led not only by the expectations of treatment effects of the study drug but also by known side effects of prednisone. Trial registration no.: NCT00973154 &nbsp.

Background: There is a lack of well-designed randomized controlled trials (RCTs) to investigate the efficacy of psychological therapies for children in foster care with emotional and behavioural difficulties. Mentalization-based therapy (MBT) focuses on supporting the carer-child relationship by promoting reflective capacity. This study examined the feasibility and acceptability of an RCT of MBT, delivered in a family-format, for children who are in foster care in the UK., Method: Herts and Minds was a phase II, blinded feasibility RCT with follow-up of at 12 and 24 weeks post-randomisation. Participants were children (age 5-16) in foster care referred to a targeted mental health service, who had some level of difficulty as identified by the Strengths and Difficulties Questionnaire (SDQ). Aims were to assess: the feasibility of recruitment processes and study uptake; capacity to train mental health practitioners to deliver MBT to an acceptable level of treatment integrity; establish acceptability and credibility of MBT as an intervention for children in foster care; establish feasibility and acceptability to participants of conducting an RCT; and estimate the likely treatment efficacy effect size. Participants were randomly allocated to either MBT (n = 15) or Usual Clinical Care (UCC) (n = 21) individually or in sibling groups. A range of qualitative and quantitative data was gathered to assess feasibility., Results: Feasibility was established with regard to: capacity to recruit participants to a study; capacity to train mental health practitioners to deliver MBT to an acceptable level of treatment integrity; acceptability and credibility of MBT; and feasibility and acceptability to participants of conducting an RCT. A number of issues made it difficult to estimate a likely treatment efficacy effect size., Conclusion: With modifications, it is feasible to run an RCT of MBT for children in foster care. Both the therapy and research design were acceptable to participants, but modifications may be needed regarding both the timing of assessments and the identification of appropriate primary outcome measures. Given the lack of evidenced based therapies for this population, such a trial would be a significant contribution to the field. Findings may be useful for other groups planning clinical trials of psychological therapies for children in foster care., Trial Registration: ISRCTN 90349442 . The trial was retrospectively registered on 6 May 2016.

Objective: We tested the hypothesis that participants who know the behavioral focus of a study and are thus aware that a particular behavior is being studied will modify that behavior, independently of any possible effect of assessment, thereby dismantling a Hawthorne effect into two putative components., Study Design and Setting: We undertook a three-arm individually randomized trial online among students: group A (control) were told they were completing a lifestyle survey; group B were told the focus of the survey was alcohol consumption; and group C additionally answered 20 questions on their alcohol use and its consequences before answering the same lifestyle questions as Groups A and B. Nondrinkers were excluded, and all groups were aware they would be followed up after 1 month., Results: Outcome data were obtained for 4,583 of 5,478 trial participants (84% follow-up rate). There were no differences between the three groups on primary (overall volume consumed) or secondary outcome measures (drinking frequency and amount per typical occasion) in the intervening 4 weeks., Conclusions: There is no evidence that any form of Hawthorne effect exists in relation to self-reported alcohol consumption online among university students in usual research practice. Attention to study contexts is warranted for investigating research participation effects., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Clinical trial accrual is vital to advancing care. A single study elucidated demographic data correlating with glioma patients' clinical trial enrollment. However, it did not investigate the underlying decision-making process for non-participation. In this study, we seek to understand this key aspect of patient accrual. All notes for glioma patients seen by a single neuro-oncologist from July 2010 to May 2017 were examined for mention of clinical trial offerings. When a trial was declined, the patient's reasoning was recorded along with the following: diagnosis, KPS, extent of resection, age, gender, race, marital status, income group, religion, trial offered at initial visit versus subsequent, and distance from trial site. Of 279 consecutive glioma patients, 88 were eligible for and offered a clinical trial. Fifty-seven accepted (65%), and 31 (35%) declined participation (Fig. 1). Of those offered a clinical trial, patients with glioblastoma (GBM) were significantly more likely to accept (44 out of 57 (77%) vs. 13 out of 57 (23%), p =0.03). After we adjusted for gender and travel distance, GBM was the only significant predictor of clinical trial acceptance, with an odds ratio of 3.18 (95% CI 1.17, 8.61, p =0.02). Reasons cited for non-participation included: travel distance (39%), lack of interest (39%), visit frequency (16%), and fear of randomization (6%). This study clarified for the first time individual glioma patient rationale for non-participation and potential areas for improving enrollment. Allowing off-site treatment centers or telemedicine visits may entice rural patients to participate. Visit frequency should be carefully considered and minimized whenever possible. Further prospective study of rationale for non-participation may improve enrollment over time.

Introduction: Randomized trials are important for generating high-quality evidence, but are perceived as difficult to perform in the pediatric population. Thus far there has been poor characterization of the barriers to conducting trials involving children, and the variation in these barriers between countries remains undescribed. The General Anesthesia compared to Spinal anesthesia (GAS) trial, conducted in seven countries between 2007 and 2013, provides an opportunity to explore these issues., Methods: We undertook a descriptive analysis to evaluate the reasons for variation in enrollment between countries in the GAS trial, looking specifically at the number of potential subjects screened, and the subsequent application of four exclusion criteria that were applied in a hierarchical order., Results: A total of 4023 patients were screened by 28 centers in seven countries. Australia and the USA screened the most subjects, accounting for 84% of all potential trial participants. The percentage of subjects eliminated from the screened pool by each exclusion criterion varied between countries. Exclusion due to a predefined condition (H1) eliminated only 5% of potential subjects in Italy and the UK, but 37% in Canada. Exclusions due to a contraindication or a physician's refusal most impacted enrollment in Australia and the USA. The patient being "too large for spinal anesthesia" was the most commonly cited by anesthetists who refused to enroll a patient (64% of anesthetist refusals). The majority of surgeon refusals came from the USA, where surgeons preferred the patient to receive a general anesthetic. The percentage of approached parents refusing to consent ranged from a low of 3% in Italy to a high of 70% in the USA and Netherlands. The most frequently cited reason for parent refusal in all countries was a preference for general anesthesia (median: 43%, range: 32%-67%). However, a sizeable proportion of parents in all countries had a contrasting preference for spinal anesthesia (median: 25%, range: 13%-31%), and 23% of U.S. parents expressed concern about randomization., Conclusion: The GAS trial highlights enrollment challenges that can occur when conducting multicenter, international, pediatric studies. Investigators planning future trials should be aware of potential differences in screening processes across countries, and that exclusions by anesthetists and surgeons may vary in reason, in frequency, and by country. Furthermore, investigators should be aware that the U.S. centers encountered particularly high surgeon and parental refusal rates and that U.S. parents were uniquely concerned about randomization. Planning trials that address these difficulties should increase the likelihood of successfully recruiting subjects in pediatric trials., (© 2018 John Wiley & Sons Ltd.)

Background: In recent years, several reviews have addressed the effectiveness of dance therapy in dementia, healthy older adults, or the elderly in general. However, reviews regarding the effect of this therapy exclusively on patients diagnosed with Alzheimer's disease have not been found., Objective: The purpose of this study is to review the available literature describing clinical trials which explore the effects of dancing on psychological and physical outcomes, functionality, cognitive function, and quality of life in patients diagnosed with Alzheimer's disease. In addition, this review aims to assess the quality of studies that perform dance therapy interventions in these patients., Methods: This study is a systematic review of randomized and non-randomized clinical trials regarding the effect of intervention including a dancing activity in people diagnosed with Alzheimer's disease., Results: In total, the evidence for this review rests on 12 studies with a total of 349 participants. The findings of this mini-review confirm the positive effect of dance therapy on physical and cognitive function, functionality, psychological outcomes, and quality of life in people with Alzheimer's disease., Conclusion: Most of the studies implementing dance as part of the therapeutic treatment has shown to improve or slow the worsening in the quality of life of patients with Alzheimer's disease and their caregivers. Future research focused on these patients should use a more exhaustive methodology and make a more detailed description of these kind of interventions., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To understand women's preferences for permanent contraception by salpingectomy or tubal occlusion following standardized counseling and evaluate the practicality of a future randomized trial., Study Design: We invited pregnant and non-pregnant women planning permanent contraception at the University of California, Davis (UCD) and University of Tennessee (UT) Obstetrics and Gynecology clinics to participate. We enrolled women when they received routine counseling and signed procedure consent. Participants received standardized information sheets reviewing permanent contraception options based on pregnancy status then completed an anonymous survey with questions about demographics, method preference, and willingness to participate in a hypothetical randomized trial comparing salpingectomy and tubal occlusion. We evaluated predictors for salpingectomy preference using multivariable analysis., Results: From July 2015 to October 2016, we enrolled 75 women at UCD and 63 women at UT. Overall, respondents preferred salpingectomy (63.0%); among the 47 women not currently pregnant at both sites, 40 (85.1%) preferred salpingectomy, most commonly because of higher efficacy. Although population characteristics differed significantly between the sites, only UCD site (aOR 4.2; 95% CI 1.9, 9.4) and non-pregnancy status (aOR 4.2; 95% CI 1.6, 10.8) predicted preference for salpingectomy in the multivariable model. Most participants (n=84, 60.9%) would not be willing to be randomized to a theoretical trial comparing salpingectomy and tubal occlusion procedures., Conclusion: Among a diverse group of women from two different areas in the U.S. given a choice of permanent contraception methods, salpingectomy is preferred over tubal occlusion. Most women planning a permanent contraceptive procedure would not agree to a randomized comparison of these methods., Implications Statement: Salpingectomy, which offers theoretically higher efficacy and potentially greater ovarian cancer protection compared to tubal occlusion, is preferred by the majority of patients and should be offered to all women seeking permanent contraception. Differences in method choices less likely reflect the patient population and more likely the counseling provided., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Genuine uncertainty on superiority of one intervention over the other is called equipoise. Physician-investigators in randomized controlled trials (RCT) need equipoise at least in studies with more than minimal risks. Ideally, this equipoise is also present in patient-participants. In pediatrics, data on equipoise are lacking. We hypothesize that 1) lack of equipoise at enrolment among parents may reduce recruitment; 2) lack of equipoise during participation may reduce retention in patients assigned to a less favoured treatment-strategy., Methods: We compared preferences of parents/patients at enrolment, documented by a questionnaire (phase 1), with preferences developed during follow-up by an interview-study (phase 2) to investigate equipoise of child-participants and parents in the BeSt-for-Kids-study (NTR 1574). This trial in new-onset Juvenile Idiopathic Arthritis-patients consists of three strategies. One strategy comprises initial treatment with a biological disease-modifying-antirheumatic-drug (DMARD), currently not standard-of-care. Semi-structured interviews were conducted with 23 parents and 7 patients, median 11 months after enrolment., Results: Initially most parents and children were not in equipoise. Parents/patients who refused participation, regularly declined due to specific preferences. Many participating families preferred the biological-first-strategy. They participated to have a chance for this initial treatment, and would even consider stopping trial-participation when not randomized for it. Their conviction of superiority of the biological-first strategy was based on knowledge from internet and close relations. According to four parents, the physician-investigator preferred the biological-first-strategy, but the majority (n = 19) stated that she had no preferred strategy. In phase 2, preferences tended to change to the treatment actually received., Conclusions: Lack of equipoise during enrolment did not reduce study recruitment, mainly due to the fact that preferred treatment was only available within the study. Still, when developing a trial it is important to evaluate whether the physicians' research question is in line with preferences of the patient-group. By exploring so-called 'informed patient-group'-equipoise, successful recruitment may be enhanced and bias avoided. In our study, lack of equipoise during trial-participation did not reduce retention in those assigned to a less favoured option. We observed a change for preference towards treatment actually received, possibly explained by comparable outcomes in all three arms.

Objective: Although there is compelling evidence that trauma-focused cognitive behavioral therapy (TF-CBT) is an effective treatment for traumatized youth, we know less about the mechanisms contributing to symptom reduction. To improve the understanding of change mechanisms in TF-CBT, this paper investigates the possible bi-directional longitudinal relationship between changes in posttraumatic stress symptoms (PTSS), cognitions and depression in a clinical sample of traumatized youth., Methods: The study includes 79 youth (M age = 15.0 years, SD = 2.2, 74.7% girls) who received TF-CBT. The youth were assessed for PTSS, posttraumatic cognitions, and depressive symptoms at baseline, mid-treatment, post-treatment, 12 months after baseline, and 18 months after post-treatment., Results: Growth curve analyses showed that PTSS, posttraumatic cognitions and depressive symptoms decreased over time. Cross-lagged mediation analyses demonstrated that reduction in posttraumatic cognitions predicted reduction in both PTSS and depression at the subsequent measurement wave, but we did not find a clear pattern in the longitudinal relationship between PTSS and depression., Conclusions: Changes in posttraumatic cognitions mediate the therapeutic effects of TF-CBT on symptoms of posttraumatic stress and depression. Future studies should seek to tease out how clinicians can best proceed to help youth reduce their posttraumatic cognitions and thereby improve treatment outcome., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Despite having similar palliative needs to patients with lung cancer, advanced chronic obstructive pulmonary disease (COPD) patients are less likely to receive palliative care. To evaluate the effect of introducing specialized palliative care with severe to very severe COPD patients, a randomized controlled trial (RCT) was conducted in Switzerland., Aim: To explore COPD patients' recollection of the trial, their needs and the usefulness of the palliative care interventions., Design and Setting: Qualitative study with advanced COPD patients who participated in a specialized palliative care intervention, conducted in a general hospital., Method: Eighteen patients with severe to very severe COPD were interviewed about their experiences. Interviews were transcribed and thematic content analysis was performed., Results: Patients had poor recollection of the trial and difficulties understanding the palliative care intervention. No major differences were observed between patients who received the specialized intervention and those who did not. Content analysis emphasized that although they experienced disabling symptoms, participants tended to attribute their limitations to problems other than COPD and some declared that they were not sick. Patients reported restrictions due to oxygen therapy, and the burden of becoming dependent on it. This dependence resulted in intense anxiety, leading participants to focus on the present only. A strong feeling of perceived helplessness emerged from the patients' interviews., Conclusions: Our findings suggest that poor recollection and understanding of the palliative care intervention act as barriers to the conduct of clinical trials with severe and very severe COPD patients. Their cognitive difficulties, perception of COPD, functional limitations, overwhelming anxiety, focus on the present and perceived helplessness also seem to hinder the implementation of such care., Competing Interests: The authors have declared that no competing interests exist.

Objective: The aim of this study was to investigate the effects of high intensity interval training (HIIT) versus moderate intensity continuous training (MICT) in heart failure patients with reduced ejection fraction (HFrEF)., Background: Despite the well-known positive effects of exercise in heart failure patients, the best mode of exercise is still under discussion., Methods: We searched Pubmed/MEDLINE, Cochrane Central Register of Controlled Trials, PEDro data base, and SciELO (from the earliest date available to October 2017) for randomized controlled trials that evaluated the effects of HIIT versus MICT in HFrEF patients. Weighted mean differences (WMD) with 95% confidence interval (CI) were calculated, and heterogeneity was assessed using the I 2 test., Results: 13 studies met the study criteria, including 411 patients. Compared to MICT, HIIT resulted in improvement in Peak VO 2 WMD (1.35 mL·kg -1 ·min -1 95% CI: 0.03 to 2.64 N = 411). HIIT resulted in no difference in VE/VCO 2 slope WMD (-1.21 95% CI: -3.0 to 0.58 N = 135), and quality of life measured by Minnesota Living with Heart Failure questionnaire WMD (1.19 95% CI: -5.81 to 8.19 N = 79). Sub-group analyses comparing studies with and without isocaloric exercise training protocol also showed a nonsignificant difference in peak VO 2 for participants in the HIIT group compared with MICT group., Conclusions: HIIT improves peak VO 2 and should be considered as a component of care of HFrEF patients. However, its superiority versus MICT disappears when isocaloric protocols are compared. An important caveat is uncertainty and variation of actual training intensities compared to program targets., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The adverse impact of unhealthy lifestyle choices and the prescription of antipsychotic medications contribute to weight gain, poor cardiovascular health and reduced life expectancy for people with psychosis. The present study aimed to explore the acceptability and perceived outcomes of a lifestyle intervention designed to prevent or reduce weight gain in people with first-episode psychosis., Methods: This was a qualitative study using a data-driven approach. People recovering from first-episode psychosis recruited from UK early intervention services and taking part in the active arm of a randomised controlled trial of a lifestyle intervention (the InterACT trial), were interviewed using a semi-structured interview schedule. Interviews were transcribed verbatim and analysed using Framework Analysis., Results: Participants valued the collaborative and individualised approach taken by the intervention deliverers, and formed high quality relationships with them. Aspects of the intervention that were positively appraised included goal setting, social opportunities, and progress monitoring. Benefits of the intervention, including increased levels of exercise; improved diet and physical health; increased psychological wellbeing (e.g. confidence, self-esteem); and improved social relationships, were identified by participants, independent of actual weight loss., Conclusions: Future interventions should ensure that workers have the skills to form high quality relationships with users, and to individualise the intervention according to users' needs and preferences. Future trials that test healthy living interventions should consider supplementing physical outcome measures with wider psychosocial outcome assessments, in particular social relationship quality, psychological wellbeing, self-esteem and self-efficacy., Trial Registration: Current Controlled Trials: ISRCTN22581937 . Date of registration: 27 October 2010 (retrospectively registered).

Background/aims: Pediatric rare disease presents a challenging situation of high unmet need and a limited pool of potential clinical trial participants. Understanding perspectives of parents of children who have not participated in trials may facilitate approaches to optimize participation rates. The objective of this study was to explore factors associated with parental interest in enrolling children with pediatric neuromuscular disorders in clinical trials., Methods: Parents of individuals with Duchenne or Becker muscular dystrophy and spinal muscular atrophy were recruited through advocacy organizations, a registry, and clinics. These parents ( N = 203) completed a questionnaire including assessments of barriers and facilitators to clinical trial participation, parents' interest in trial participation, and their perceptions of others' views about participation in a clinical trial., Results: Trial interest in participating parents was high (64% combined group). The most highly endorsed barrier to participation was the possibility of receiving placebo, followed by not having enough information on risks and trial procedures. Compared to parents of children with Duchenne or Becker muscular dystrophy, parents of children with spinal muscular atrophy endorsed significantly more information and knowledge barriers. The greatest facilitators of participation were (1) confidence in improving disease understanding and (2) guarantee to receive the treatment after a successful trial. A logistic regression model, χ 2 (4, n = 188) = 80.64, p < .001, indicated that higher perceived barriers and more frequent trial communication by the provider were associated with lower interest, while positive trial perceptions by the child's providers and concordance in trial perceptions among those close to the decision-maker were associated with higher interest., Conclusion: We found high parental interest in pediatric neuromuscular trials that was tempered by concerns about the potential for randomization to a placebo arm. Participants perceived that their trial participation would be facilitated by additional education and guidance from their clinicians. Yet, intentions were negatively associated with frequency of provider communication, perhaps reflecting waning parental interest with a greater understanding of limitations in trial access, increased sophistication in their understanding of trial design, and appreciation of potential burden. To support parents' informed decisions, it is important to educate them to evaluate the quality of research, as well as providing lay information explaining the use of placebo, trial processes, and potential barriers to long-term drug access. Our findings should inform the development of targeted educational content, clinician training, and decision support tools.

Aim: To determine parental and clinician views of the informed consent process in neonatal research., Methods: A questionnaire-based study on the informed consent process. Two questionnaires were developed and distributed to parents and clinicians over a four-month period., Results: Thirty-four parents (79%) surveyed had consented their baby to a research study. The majority of clinicians (72%) had a preference for antenatal provision of information. A desire to help future babies (97%, n=32) and a belief that their baby's healthcare would directly benefit (72%, n=28) were primary reasons for consenting. The majority (76% n=28) of parents were not in favour of a waiver of consent. However twenty clinicians (56%) agreed that a waiver of consent may be appropriate in neonatal research. Thirty-one (86%) clinicians rated GCP training as important., Discussion: Parents are generally supportive of neonatal research. Good clinical practice training is essential for clinicians involved in neonatal research.

The relationship between stress and infertility has been debated for years. Women with infertility report elevated levels of anxiety and depression, so it is clear that infertility causes stress. What is less clear, however, is whether or not stress causes infertility. The impact of distress on treatment outcome is difficult to investigate for a number of factors, including inaccurate self-report measures and feelings of increased optimism at treatment onset. However, the most recent research has documented the efficacy of psychological interventions in lowering psychological distress as well as being associated with significant increases in pregnancy rates. A cognitive-behavioral group approach may be the most efficient way to achieve both goals. Given the distress levels reported by many infertile women, it is vital to expand the availability of these programs.

Objective: The Fluids in Shock (FiSh) Trial proposes to evaluate whether restrictive fluid bolus therapy (10 mL/kg) is more beneficial than current recommended practice (20 mL/kg) in the resuscitation of children with septic shock in the UK. This qualitative feasibility study aimed to explore acceptability of the FiSh Trial, including research without prior consent (RWPC), potential barriers to recruitment and participant information for a pilot trial., Design: Qualitative interview study involving parents of children who had presented to a UK emergency department or been admitted to a paediatric intensive care unit with severe infection in the previous 3 years., Participants: Twenty-one parents (seven bereaved) were interviewed 16 (median) months since their child's hospital admission (range: 1-41)., Results: All parents said they would have provided consent for the use of their child's data in the FiSh Trial. The majority were unfamiliar with RWPC, yet supported its use. Parents were initially concerned about the change from currently recommended treatment, yet were reassured by explanations of the current evidence base, fluid bolus therapy and monitoring procedures. Parents made recommendations about the timing of the research discussion and content of participant information. Bereaved parents stated that recruiters should not discuss research immediately after a child's death, but supported a personalised postal 'opt-out' approach to consent., Conclusions: Findings show that parents whose child has experienced severe infection supported the proposed FiSh Trial, including the use of RWPC. Parents' views informed the development of the pilot trial protocol and site staff training., Trial Registration Number: ISRCTN15244462-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: In several randomized controlled trials (RCT) acetylcholinesterase-inhibitors (AChE-I) were tested in patients with mild cognitive impairment (MCI) but were ineffective in delaying disease progression as determined by neuropsychological testing only. Here we present data from an open label observational extension of a multicenter RCT in order to assess if biomarkers are providing useful additional information about a drug's efficacy. We followed 83 amnestic MCI patients and performed correlational analyses of Aβ 1-42 and total-Tau in the cerebrospinal fluid (CSF), hippocampal and amygdala volume at baseline, the total duration of blinded and open label AChE-I treatment and the outcome 24 months after inclusion into the RCT. Twelve out of 83 amnestic MCI (14%) had progressed to Alzheimer's disease (AD). Overall, worsening and disease progression as measured by the Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog), Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) and Clinical Dementia Rating (CDR) did not correlate with the duration of AChE-I treatment. However, a specific multidimensional biomarker profile at baseline indicated more reliably than cognitive testing alone progression to AD. We conclude that pharmacological RCTs testing symptomatic treatment effects in MCI should include biomarker assessment.

The present paper reviews how language and communication are used to describe placebo phenomena in medicine, with particular reference at key points to the question of pain. Selected aspects of placebo language are submitted to lexical, grammatical and semantic analysis. We distinguish three uses of placebo, with three semantic components: "pleasing," inert medication or procedure, and what is often called "deception." The three uses of placebo are: Placebo-treatment, which combines all three semantic components: "pleasing" patients with inert treatments, and possibly with "deception." Placebo-trial, which refers to the closely defined inert control in Randomized Controlled Trials. Placebo-rapport, which covers all aspects of the health care encounter, excluding therapeutic interventions, but including psychosocial factors which can have a beneficial effect on the patient. Three key conclusions emerge from this analysis. First, the "deception" connotation of placebo found in placebo-treatment can contaminate the use of placebo-trial and especially placebo-rapport. Second, the enlarged "pleasing" framework of placebo-rapport, which includes the benefits of quality appropriate and helpful medical care, forces us to ask whether placebo-trial in Randomized Controlled Trials has in fact been a neutral baseline control. Biopsychosocial and other factors in placebo-rapport may have influenced the outcomes of many trials in medicine and pharmacology. And third, extending placebo-rapport to embrace all aspects of clinical care (except specific medication or procedural interventions) and psychosocial factors of the health care encounter engages patient beliefs, mindsets and interpersonal dynamics, as well as values and contextual and cultural issues. These take placebo-rapport substantially beyond what is currently seen as its identity and modes of operation., (© 2018 Elsevier Inc. All rights reserved.)

Background: This study sought to establish the preferences of people with Rheumatoid Arthritis (RA) about the best outcome measure for a health and fitness intervention randomised controlled trial (RCT). The results of this study were used to inform the choice of the trial primary and secondary outcome measure., Methods: A discrete choice experiment (DCE) was used to assess people's preferences regarding a number of outcomes (foot and ankle pain, fatigue, mobility, ability to perform daily activities, choice of footwear) as well as different schedules and frequency of delivery for the health and fitness intervention. The outcomes were chosen based on literature review, clinician recommendation and patients' focus groups. The DCE was constructed in SAS software using the D-efficiency criteria. It compared hypothetical scenarios with varying levels of outcomes severity and intervention schedule. Preference weights were estimated using appropriate econometric models. The partial log-likelihood method was used to assess the attribute importance., Results: One hundred people with RA completed 18 choice sets. Overall, people selected foot and ankle pain as the most important outcome, with mobility being nearly as important. There was no evidence of differential preference between intervention schedules or frequency of delivery., Conclusions: Foot and ankle pain can be considered the patient choice for primary outcome of an RCT relating to a health and fitness intervention. This study demonstrated that, by using the DCE method, it is possible to incorporate patients' preferences at the design stage of a RCT. This approach ensures patient involvement at early stages of health care design., Competing Interests: The study was approved by the research governance committee of the Department of Health Sciences, University of York.Not applicable.The authors declare they have no conflict of interest.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Objectives: Yoga may improve stress, affect, and weight control, all of which are commonly cited barriers to quitting smoking. However, the importance of these concerns may vary by sex, race, ethnicity, and age. We examined smoking-relevant characteristics of individuals enrolling in an 8-week randomized controlled trial testing yoga as a complementary treatment to standard smoking cessation., Methods: Of 958 callers, 227 were eligible and enrolled., Results: The sample was 55% female, 86% non-Hispanic white, with a mean age of 46 years (SD = 12). Males smoked more cigarettes/ day than females and had lower motivation to quit smoking. Females were more likely to smoke for weight control, social and mood-related reasons, and had higher expectations for the efficacy of yoga. Age was negatively associated with the presence of other smokers in the household, and smoking in response to negative moods, and was positively associated with smoking rate, and confidence in quitting., Conclusions: This study demonstrated that both males and females were interested in a program offering yoga as a complementary therapy for smoking cessation. However, there were both sex and age-related differences with respect to smoking-related variables that may suggest a need to adapt the intervention for sub-populations.

Background: Medication development for alcoholism typically includes experimental pharmacology studies with non-treatment-seeking individuals with alcohol use disorder (AUD) paving the way for randomized controlled trials in treatment-seekers with AUD., Objectives: The goal of this study is to provide a direct comparison between AUD treatment-seeking research participants and non-treatment-seeking participants on demographic and clinical variables and to test whether variables that differentiate the two groups are associated with clinical outcomes., Method: Non-treatment-seeking AUD participants (n = 213; 76.3% male) who completed behavioral pharmacology studies were compared to treatment-seekers who completed the COMBINE Study (n = 1383; 69.1% male) on demographic and clinical variables. Analyses examined whether the variables that differentiated the two groups predicted treatment outcomes in the COMBINE Study., Results: Analyses revealed that treatment-seeking participants were older, had more years of education, higher Alcohol Dependence Scale scores, higher Drinker Inventory of Consequences scores, higher Obsessive Compulsive Drinking Scale scores, a greater number of DSM-IV symptoms of AUD, longer duration of AUD, and consumed more standard drinks and more drinks per drinking day (i.e., in the past 30 days) compared to non-treatment-seeking participants. Nearly all characteristics that differed between the groups predicted at least one of the primary clinical outcomes of the COMBINE Study., Conclusions: This study highlights a host of clinical and demographic factors that differ between non-treatment-seeking and treatment-seeking research participants and the clinical significance of these variables. Differences between samples should be considered and addressed in order to promote greater consilience across stages of medication development.

Background: As an important part of a pilot study to determine the feasibility of a large randomised controlled trial (RCT) comparing use of the Manchester Acute Coronary Syndromes (MACS) decision rule with standard care, we aimed to explore patient attitudes and potential barriers to participation in a trial of this nature., Methods: We conducted a qualitative study nested within a pilot RCT comparing use of the MACS rule (which could enable some patients with chest pain to be discharged earlier) with standard care. Semi-structured interviews with consenting participants were conducted with reference to a bespoke topic guide. Interviews were audio recorded, transcribed verbatim and analysed using the Framework method with an inductive approach., Results: The 10 interviewees expressed that participation in the trial was generally acceptable. All but one recommended participation to others. Participants who were in pain or anxious at the time of arrival reported that the initial invitation to participate in the trial was sometimes made too early. The approach was welcome, providing they had been given time to settle. Interviewees welcomed the opportunity that trial participation offered for them to play a more active role in their healthcare and to reduce unnecessary waiting time. Participants appeared to like the fact that participation in the trial might mean they could return home sooner and welcomed the provision of follow-up. Although several participants described being generally sceptical of medical research, they were amenable to participation in this trial. This appears to be because they agreed with the need for research in this field and perceived the intervention as non-invasive., Conclusions: Patients were positive about their participation in this RCT comparing the MACS rule with standard care. A number of areas for improving trial design were identified and should be considered in the planning of future large trials., Trial Registration: ISRCTN 86818215 RESEARCH ETHICS COMMITTEE REFERENCE: 13/NW/0081 UKCRN REGISTRATION ID: 14334., Competing Interests: Competing interests: RB has previously undertaken research involving donation of reagents without charge by Roche, Abbott, Alere, Siemens and Randox. He has accepted the provision of economy class travel and accommodation to present findings unrelated to this work at two Roche-sponsored conferences and at a scientific session sponsored by Randox., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Context: Family members of critically ill patients who participate in research focused on palliative care issues have been found to be systematically different from those who do not. These differences threaten the validity of research and raise ethical questions about worsening disparities in care by failing to represent diverse perspectives., Objectives: This study's aims were to explore: 1) barriers and facilitators influencing family members' decisions to participate in palliative care research; and 2) potential methods to enhance research participation., Methods: Family members who were asked to participate in a randomized trial testing the efficacy of a facilitator to improve clinician-family communication in the intensive care unit (ICU). Family members who participated (n = 17) and those who declined participation (n = 7) in Family Communication Study were interviewed about their recruitment experiences. We also included family members of currently critically ill patients to assess current experiences (n = 4). Interviews were audio-recorded and transcribed. Investigators used thematic analysis to identify factors influencing family members' decisions. Transcripts were co-reviewed to synthesize codes and themes., Results: Three factors influencing participants' decisions were identified: Altruism, Research Experience, and Enhanced Resources. Altruism and Research Experience described intrinsic characteristics that are less amenable to strategies for improving participation rates. Enhanced Resources reflects families' desires for increased access to information and logistical and emotional support., Conclusion: Family members found their recruitment experiences to be positive when staff were knowledgeable about the ICU, sensitive to the stressful circumstances, and conveyed a caring attitude. By training research staff to be supportive of families' emotional needs and need for logistical knowledge about the ICU, recruitment of a potentially more diverse sample of families may be enhanced., (Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Distributed cognition occurs when cognitive and affective schemas are shared between two or more people during interpersonal discussion. Although extant research focuses on distributed cognition in decision making between health care providers and patients, studies show that caregivers are also highly influential in the treatment decisions of patients. However, there are little empirical data describing how and when families exert influence. The current article addresses this gap by examining decisional support in the context of cancer randomized clinical trial (RCT) decision making. Data are drawn from in-depth interviews with rural, Appalachian cancer patients ( N = 46). Analysis of transcript data yielded empirical support for four distinct models of health decision making. The implications of these findings for developing interventions to improve the quality of treatment decision making and overall well-being are discussed.

Background: Discussing randomized clinical trials (RCTs) with cancer patients is one of the most challenging communication tasks a physician faces. Only two prior Communication Skills Trainings (CSTs) focused on RCTs in oncology have been reported. Their results demonstrated the need for further improvement. We developed and evaluated an enhanced, individually-tailored CST focused on improving physicians' communication during discussions of RCTs., Methods: The CST focused on personal learning goals derived from video pre-assessment that were addressed in a 1.5-day group workshop and one-on-one coaching sessions. Forty physicians were recruited and randomly assigned to intervention and control groups. Video-recorded standardized consultations with actor-patients were utilized. As a primary outcome (1), training success was evaluated by blinded raters using a previously developed checklist. Change in checklist items was evaluated between pre- and post-training assessment and compared against control group results. As a secondary outcome (2), the physicians' feeling of confidence was assessed by a questionnaire., Results: (1) Significant improvements in the intervention group were observed for the score on all items (p = 0.03), for the subgroup of content-specific items (p = 0.02), and for the global rating of communication competence (p = 0.04). The improvement observed for the subgroup of general communication skill items did not achieve significance (p = 0.20). (2) The feeling of confidence improved in nine out of ten domains., Conclusion: While the individually-tailored CST program significantly improved the physicians' discussions of RCTs, specifically related to discussion content, what remains unknown is the influence of such programs in practice on participant recruitment rates. The study was registered retrospectively in 2010/07/22 under DRKS-ID: DRKS00000492 .

Purpose: Challenges can arise when attempting to maximize patient enrollment in clinical trials. There have been limited studies focusing on the barriers to enrollment and the efficacy of alternative study design to improve accrual. We analyzed barriers to clinical trial enrollment, particularly the influence of timing, in context of three prospective, randomized oncology trials where one arm was considered more aggressive than the other., Methods and Materials: From June 2011 to March 2015, patients who were enrolled on 3 prospective institutional protocols (an oligometastatic non-small cell lung cancer [NSCLC] trial and 2 proton vs intensity modulated radiation therapy trials in NSCLC and esophageal cancer) were screened for protocol eligibility. Eligible candidates were approached about trial participation, and patient characteristics (age, sex, T/N categorization) were recorded along with details surrounding trial presentation (appointment number). Fisher's exact test, Student's t tests, and multivariate analysis were performed to assess differences between enrolled and refusal patients., Results: A total of 309 eligible patients were approached about trial enrollment. The enrollment success rate during this time span was 52% (n=160 patients). Enrolled patients were more likely to be presented trial information at an earlier appointment (oligometastatic protocol: 5 vs 3 appointments [P<.001]; NSCLC protocol: 4 vs 3 appointments [P=.0018]; esophageal protocol: 3 vs 2 appointments [P=.0086]). No other factors or patient characteristics significantly affected enrollment success rate., Conclusion: Improvement in enrollment rates for randomized control trials is possible, even in difficult accrual settings. Earlier presentation of trial information to patients is the most influential factor for success and may help overcome accrual barriers without compromising trial design., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Minority recruitment to cancer trials is low and there are limited data on minority adherence to lifestyle modification interventions. We examined factors related to recruitment and adherence to a pilot weight loss intervention among Hispanic and black breast cancer survivors. Participants completed a detailed screening interview to assess barriers to enrollment. An index was created to assess adherence at 6 months. 112 potentially eligible women were identified; 66 consented and completed a screening interview. After screening, 9 were ineligible; 15 opted to not enroll; and 42 were randomized. Among eligible women, earlier stage at diagnosis, treatment type, and negative beliefs related to exercise and diet after diagnosis were negatively associated with study enrollment (P < 0.05). Self-reported barriers to adherence included fatigue, family responsibilities, illness, work, transportation, and negative perceptions of exercise and diet. Results from this study emphasize the need to adapt recruitment and adherence strategies to address these factors.

Objective: This secondary data analysis examined patterns of drinking during alcohol treatment and associated drinking outcomes during the first year following treatment. The goal was to provide clinicians with guidance on which patients may be most at risk for negative long-term outcomes based on drinking patterns during treatment., Method: This study was an analysis of existing data (N = 3,851) from three randomized clinical trials for alcohol use disorder: the COMBINE Study (n = 1,383), Project MATCH (n = 1,726), and the United Kingdom Alcohol Treatment Trial (n = 742). Indicators of abstinence, non-heavy drinking, and heavy drinking (defined as 4/5 or more drinks per day for women/men) were examined during each week of treatment using repeated-measures latent class analysis. Associations between drinking patterns during treatment and drinking intensity, drinking consequences, and physical and mental health 12 months following intake were examined., Results: Seven drinking patterns were identified. Patients who engaged in persistent heavy drinking throughout treatment and those who returned to persistent heavy drinking during treatment had the worst long-term outcomes. Patients who engaged in some heavy drinking during treatment had better long-term outcomes than persistent heavy drinkers. Patients who reported low-risk drinking or abstinence had the best long-term outcomes. There were no differences in outcomes between low-risk drinkers and abstainers., Conclusions: Abstinence, low-risk drinking, or even some heavy drinking during treatment are associated with the best long-term outcomes. Patients who are engaging in persistent heavy drinking are likely to have the worst outcomes and may require a higher level of care.

Background: Individual informed consent from all participants is required for most randomized clinical trials (RCTs). However, some exceptions-for example, emergency research-are widely accepted., Methods: The literature on various approaches to randomization without consent (RWOC) has never been systematically reviewed. Our goal was to provide a survey and narrative synthesis of published proposals for RWOC. We focused on proposals to randomize at least some participants in a study without first obtaining consent to randomization. This definition included studies that omitted informed consent entirely, omitted informed consent for selected patients (e.g., the control group), obtained informed consent to research but not to randomization, or only obtained informed consent to randomization after random assignment had already occurred. It omitted oral and staged consent processes that still obtain consent to randomization from all participants before randomization occurs., Results: We identified ten different proposals for RWOC: two variants of cluster randomization, two variants of the Zelen design, consent to postponed information, two-stage randomized consent, cohort multiple RCT, emergency research, prompted optional randomization trials, and low-risk pragmatic RCTs without consent., Conclusion: Of all designs discussed here, only cluster randomized designs and emergency research are routinely used, with the justification that informed consent is infeasible in those settings. Other designs have raised concerns that they do not appropriately respect patient autonomy. Recent proposals have emphasized the importance for RWOC of demonstrating such respect through systematic patient engagement, transparency, and accountability, potentially in the context of learning health care systems.

High retention and treatment adherence are essential to ensure the quality of evidence from clinical trials. Strategies for improving these have been explored but actual rates in lifestyle intervention trials indicate challenges. This study examined the use of a motivational interviewing-informed strategy during interactive group orientations prior to obtaining informed consent, collecting baseline data and randomization in a healthy dietary pattern intervention trial for asthma control in adults. The themes generated from small group discussions and echoed in large group discussions during the orientation sessions helped potential participants better understand the scientific rationale of the research design and procedures and the practical implications for them to participate in the study. Potential participants reported significantly lower confidence of completing the study after the group orientation. This suggests that the group orientations helped potential participants identify challenges to completing the study, have more realistic expectations about participation and be prepared if enrolled. Both retention (92% of 90 participants at 6 months) and intervention attendance (99% of 46 intervention participants attended 80% of 11 weekly group/individual sessions) were high, suggesting the motivation interviewing-informed group orientation strategy may help improve retention and adherence in clinical trials., (© The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Barber and Muenz (1996) reported that cognitive behavior therapy (CBT) was more effective than interpersonal therapy (IPT) for depressed patients with elevated levels of avoidant personality disorder, while IPT was more effective than CBT in patients with elevated levels of obsessive-compulsive personality disorder. These findings may have important clinical implications, but have not yet been replicated., Methods: We conducted a study using data from a randomized clinical trial comparing the efficacy of CBT and short-term psychodynamic supportive psychotherapy in the outpatient treatment of depression., Results: We found no evidence indicating that avoidant patients may benefit more from CBT compared to short-term psychodynamic supportive therapy (SPSP)., Conclusions: Our results indicate that treatment effect does not depend on the level of avoidance, or obsessive-compulsiveness personality disorders further examine the influence of personality disorders on the effectiveness of CBT or psychodynamic therapy in the treatment of depression., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: To evaluate gynecologic oncology patients' perceptions and willingness to participate in randomized clinical trials (RCT) among an inner city population., Methods: Informed consent was obtained. Demographics were collected and willingness to participate in a RCT was measured by the Attitudes on Randomized Trials Questionnaire (ARTQ). The Hospital Anxiety and Depression Scale estimated levels of anxiety and depression. A Perception Survey was created and tested as a screening tool for patients considering RCTs. Standard statistical tests were used., Results: One hundred and one women participated, 54 (53.5%) were black, 31 (30.7%) were white, non-Hispanic and 15 (14.9%) were Hispanic. Screening for anxiety and depression revealed an 18.8% rate of moderate to severe anxiety and an 11.9% rate of moderate to severe depression. Willingness to participate in a RCT as measured by ARTQ scores was not significantly associated with race, levels of anxiety or depression. Twenty-eight percent of women would agree to participate in a clinical trial at baseline. An additional, 33 (32.7%), for a total of 61.4%, indicated agreement after targeted education with no statistical differences by race or psychological stressor. However, sixty-one percent of these women were black. The Perception Survey approximated the results of the ARTQ with reasonable accuracy (AUC 0.758, p<0.001) CONCLUSIONS: Neither race nor psychological stressor were significant indicators of willingness to participate in a RCT. Targeted education resulted in a majority of patients indicating willingness to participate in trials, especially among black women. Additionally, a novel screening tool was tested and performed well in this setting., (Copyright © 2016. Published by Elsevier Inc.)

Background: Randomized clinical trials (RCTs), mostly conducted among minority populations, have reported that motivational interviewing (MI) can improve medication adherence., Objectives: To evaluate the impact of MI and of the MI delivery format, fidelity assessment, fidelity-based feedback, counselors' background and MI exposure time on adherence., Data Sources: We searched the MEDLINE database for studies published from 1966 until February 2015., Study Eligibility Criteria: We included RCTs that compared MI to a control group and reported a numerical measure of medication adherence., Data Synthesis: The main outcome was medication adherence defined as any subjective or objective measure reported as the proportion of subjects with adequate adherence or mean adherence and standard deviation. For categorical variables we calculated the relative risk (RR) of medication adherence, and for continuous variables we calculated the standardized mean difference (SMD) between the MI and control groups., Results: We included 17 RCTs. Ten targeted adherence to HAART. For studies reporting a categorical measure (n = 11), the pooled RR for medication adherence was higher for MI compared with control (1.17; 95 % CI 1.05- 1.31; p < 0.01). For studies reporting a continuous measure (n = 11), the pooled SMD for medication adherence was positive (0.70; 95 % CI 0.15-1.25; p < 0.01) for MI compared with control. The characteristics that were significantly (p < 0.05) associated with medication adherence were telephonic MI and fidelity-based feedback among studies reporting categorical measures, group MI and fidelity assessment among studies reporting continuous measures and delivery by nurses or research assistants. Effect sizes differed in magnitude, creating high heterogeneity., Conclusion: MI improves medication adherence at different exposure times and counselors' educational level. However, the evaluation of MI characteristics associated with success had inconsistent results. Larger studies targeting diverse populations with a variety of chronic conditions are needed to clarify the effect of different MI delivery modes, fidelity assessment and provision of fidelity based-feedback.

Background: Current guidelines advise providers to assess smokers' readiness to quit, then offer cessation therapies to smokers planning to quit and motivational interventions to smokers not planning to quit., Objectives: We examined the relationship between baseline stage of change (SOC), treatment utilization, and smoking cessation to determine whether the effect of a proactive smoking cessation intervention was dependent on smokers' level of motivation to quit., Design: Secondary analysis of a multicenter randomized controlled trial., Participants: A total of 3006 current smokers, aged 18-80 years, at four Veterans Affairs (VA) medical centers., Interventions: Proactive care included proactive outreach (mailed invitation followed by telephone outreach), offer of smoking cessation services (telephone or face-to-face), and access to pharmacotherapy. Usual care participants had access to VA smoking cessation services and state telephone quitlines., Main Measures: Baseline SOC measured with Readiness to Quit Ladder, and 6-month prolonged abstinence self-reported at 1 year., Key Results: At baseline, 35.8 % of smokers were in preparation, 38.2 % in contemplation, and 26.0 % in precontemplation. The overall interaction between SOC and treatment arm was not statistically significant (p = 0.30). Among smokers in preparation, 21.1 % of proactive care participants achieved 6-month prolonged abstinence, compared to 13.1 % of usual care participants (OR, 1.8 [95 % CI, 1.2-2.6]). Similarly, proactive care increased abstinence among smokers in contemplation (11.0 % vs. 6.5 %; OR, 1.8 [95 % CI, 1.1-2.8]). Smokers in precontemplation quit smoking at similar rates (5.3 % vs. 5.6 %; OR, 0.9 [95 % CI, 0.5-1.9]). Within each stage, uptake of smoking cessation treatments increased with higher SOC and with proactive care as compared with usual care., Limitations: Mostly male participants limits generalizability. Randomization was not stratified by SOC., Conclusions: Proactive care increased treatment uptake compared to usual care across all SOC. Proactive care increased smoking cessation among smokers in preparation and contemplation but not in precontemplation. Proactively offering cessation therapies to smokers at all SOC will increase treatment utilization and population-level smoking cessation.