Widening participation - recruitment methods in mental health randomised controlled trials: a qualitative study.

BACKGROUND: Barriers to mental health research participation are well documented including distrust of services and research; and stigma surrounding mental health. They can contribute to a lack of diversity amongst participants in mental health research, which threatens the generalisability of knowledge. Given the recent widespread use of the internet in medical research, this study aimed to explore the perspectives of key partners on the use of online (e.g. social media) and offline (e.g. in-person) recruitment as an approach to improving diversity in mental health randomised controlled trials (RCTs). METHODS: Face-to-face and online interviews/focus groups with researchers working in mental health and Patient and Public Involvement partners in the United Kingdom. Recordings were transcribed and analysed using a combination of inductive and deductive thematic analysis. RESULTS: Three focus groups and three interviews were conducted with a total N = 23 participants. Four overarching themes were identified: (1) recruitment reach; (2) Demographic factors that affect selection of recruitment method; (3) safety of technology, and; (4) practical challenges. Five main factors were identified that affect the choice of recruitment method: age, complexity of mental health problem and stigma, cultural and ethnicity differences and digital divide. The use of online methods was considered more accessible to people who may feel stigmatised by their mental health condition and with a benefit of reaching a wider population. However, a common view amongst participants was that online methods require closer data monitoring for quality of responders, are not fully secure and less trustworthy compared to offline methods that enable participants to build relationships with health providers. Funding, staff time and experience, organisational support, and technical issues such as spam or phishing emails were highlighted as practical challenges facing online recruitment. All participants agreed that using a hybrid approach tailored to the population under study is paramount. CONCLUSIONS: This study highlighted the importance of offering a flexible and multifaceted recruitment approach by integrating online with offline methods to support inclusivity and widening participation in mental health research. The findings will be used to develop considerations for researchers designing RCTs to improve recruitment in mental health research.

High-Stakes Collaborative Testing: Why Not?

Phenomenon: Studies of high-stakes collaborative testing remain sparse, especially in medical education. We explored high-stakes collaborative testing in medical education, looking specifically at the experiences of students in established and newly formed teams. APPROACH: Third-year psychiatry students at 5 medical schools across 6 sites participated, with 4 participating as established team sites and 2 as comparison team sites. For the collaborative test, we used the National Board of Medical Examiners Psychiatry subject test, administering it via a 2-stage process. Students at all sites were randomly selected to participate in a focus group, with 8-10 students per site (N = 49). We also examined quantitative data for additional triangulation. FINDINGS: Students described a range of heightened emotions around the collaborative test yet perceived it as valuable regardless if they were in established or newly formed teams. Students described learning about the subject matter, themselves, others, and interpersonal dynamics during collaborative testing. Triangulation of these results via quantitative data supported these themes. Insights: Despite student concerns, high-stakes collaborative tests may be both valuable and feasible. The data suggest that high-stakes tests (tests of learning or summative evaluation) could also become tests for learning or formative evaluation. The paucity of research into this methodology in medical education suggests more research is needed.

Team cohesiveness, team size and team performance in team-based learning teams.

OBJECTIVES: The purpose of this study was to explore the relationships among variables associated with teams in team-based learning (TBL) settings and team outcomes. METHODS: We administered the National Board of Medical Examiners (NBME) Psychiatry Subject Test first to individuals and then to teams of Year three students at four medical schools that used TBL in their psychiatry core clerkships. Team cohesion was analysed using the Team Performance Scale (TPS). Bivariate correlation and linear regression analysis were used to analyse the relationships among team-level variables (mean individual TPS scores for each team, mean individual NBME scores of teams, team size, rotation and gender make-up) and team NBME test scores. A hierarchical linear model was used to test the effects of individual TPS and individual NBME test scores within each team, as well as the effects of the team-level variables of team size, team rotation and gender on team NBME test scores. Individual NBME test and TPS scores were nested within teams and treated as subsampling units. RESULTS: Individual NBME test scores and individual TPS scores were positively and statistically significantly (p < 0.01) associated with team NBME test scores, when team rotation, team size and gender make-up were controlled for. Higher team NBME test scores were associated with teams rotating later in the year and larger teams (p < 0.01). Gender make-up was not significantly associated. CONCLUSIONS: The results of an NBME Psychiatry Subject Test administered to TBL teams at four medical schools suggest that larger teams on later rotations score higher on a team NBME test. Individual NBME test scores and team cohesion were positively and significantly associated with team NBME test scores. These results suggest the need for additional studies focusing on team outcomes, team cohesion, team size, rotation and other factors as they relate to the effective and efficient performance of TBL teams in health science education.

Team Emotional Intelligence, Team Interactions, and Gender in Medical Students During a Psychiatry Clerkship.

OBJECTIVE: This study examined the relationship between team emotional intelligence, quality of team interactions, and gender. METHODS: Psychiatry clerkship students participating in Team-Based Learning (TBL, n = 484) or no TBL (control, n = 265) completed the Workgroup Emotional Intelligence Profile (WEIP-S) and the Team Performance Scale (TPS). RESULTS: Significant correlations (p < 0.01) existed between quality of team interactions (i.e., TPS) and team emotional intelligence (i.e., WEIP-S) subscales, but not gender. Control and TBL groups experienced significant increases in WEIP-S subscales pre to post (p < 0.01, η (2) = .08), with the TBL group experiencing significantly higher gains in three of four subscales. Control group scored higher on TPS. CONCLUSIONS: A significant relationship exists between team emotional intelligence and quality of team interactions. Gender was unrelated to TPS or WEIP-S subscales. TBL group experienced higher gains in WEIP-S subscales while the control group experienced slightly higher TPS scores. Results suggest implications for medical educators who use TBL.

Using online methods to recruit participants into mental health clinical trials: considerations and recommendations from the RE-MIND study.

BACKGROUND: Ensuring diversity in clinical trials can be a challenge, which may be exacerbated when recruiting vulnerable populations, such as participants with mental health illness. As recruitment continues to be the major cause of trial delays, researchers are turning to online recruitment strategies, e.g. social media, to reach a wider population and reduce recruitment time and costs. There is mixed evidence for the use of online recruitment strategies; therefore, the REcruitment in Mental health trials: broadening the 'net', opportunities for INclusivity through online methoDs (RE-MIND) study aimed to identify evidence and provide guidance for use of online strategies in recruitment to mental health trials, with a focus on whether online strategies can enhance inclusivity. This commentary, as part of the RE-MIND study, focusses on providing recommendations for recruitment strategy selection in future research with the aim to improve trial efficiency. A mixed-methods approach was employed involving three work packages: (I) an evidence review of a cohort of 97 recently published randomised controlled trials/feasibility or pilot studies in mental health to assess the impact of online versus offline recruitment; (II) a qualitative study investigating the experiences of n = 23 key stakeholders on use of an online recruitment approach in mental health clinical trials; (III) combining the results of WP1 and WP2 to produce recommendations on the use of an online recruitment strategy in mental health clinical trials. The findings from WP1 and 2 have been published elsewhere; this commentary represents the results of the third work package. CONCLUSION: For external validity, clinical trial participants should reflect the populations that will ultimately receive the interventions being tested, if proven effective. To guide researchers on their options for inclusive recruitment strategies, we have developed a list of considerations and practical recommendations on how to maximise the use of online recruitment methods.

The Effect of Gender on Team-Based Learning Peer Assessment in a Psychiatry Clerkship.

In team-based learning (TBL), peer evaluation is important, but also open to bias. We examined the relation between gender and summative peer feedback over 3 years in all 90 teams created in our psychiatry clerkship. Gender-equivalent (92.7 vs 88.1, p < 0.05) and majority-women (93.6 vs 88.1, p < 0.05) teams scored higher than majority-men in the first 2 years, as did women-majority teams in the third (98.3 vs 94.8, p < 0.05). Mean scores were little-affected by team size. These findings suggest TBL team gender balance can adversely affect peer evaluations. Instructors should consider team gender composition and the weight given to feedback scores.

Hyperbaric oxygen therapy for mild traumatic brain injury persistent postconcussion syndrome: a randomized controlled trial.

Persistent postconcussion syndrome (PPCS) after mild traumatic brain injury (mTBI) is a significant public health and military problem for which there is limited treatment evidence. The aim of this study was to determine whether forty 150 kPa hyperbaric oxygen therapies (HBOTs) can improve symptoms and cognitive function in subjects with the PPCS of mTBI, using a randomized controlled crossover design with 2-month follow-up. Sixty-three civilian and military subjects with mTBI/PPCS were randomized to either 40 HBOTs at 150 kPa/60 minutes, once daily, 5 days per week in 8 weeks or an equivalent no-treatment control period. The Control Group was then crossed over to HBOT. Subjects underwent symptom, neuropsychological, and psychological testing, before and after treatment or control with retesting 2 months after the 40th HBOT. Fifty subjects completed the protocol with primary outcome testing. HBOT subjects experienced significant improvements in Neurobehavioral Symptom Inventory, Memory Index, Automated Neuropsychological Assessment Metrics, Hamilton Depression Scale, Hamilton Anxiety Scale, Post-Traumatic Stress Disorder Checklist, Pittsburgh Sleep Quality Index, and Quality Of Life after Brain Injury compared to the Control Group. After crossing over to HBOT the Control Group experienced near-identical significant improvements. Further improvements were experienced by both groups during the 2-month follow-up period. These data indicate that 40 HBOTs at 150 kPa/60 minutes demonstrated statistically significant improvements in postconcussion and Post-Traumatic Stress Disorder symptoms, memory, cognitive functions, depression, anxiety, sleep, and quality of life in civilian and military subjects with mTBI/PPCS compared to controls. Improvements persisted at least 2 months after the 40th HBOT. The study was registered on ClinicalTrials.gov (NCT02089594) on March 18, 2014 and with the U.S. Food and Drug Administration under Investigational New Drug #113823. The Institutional Review Boards of the United States Army Medical Research and Materiel Command Office of Research Protections Human Research Protection Office and the Louisiana State University School of Medicine (approval No. 7381) approved the study on May 13, 2014 and December 20, 2013, respectively.

Opportunities and challenges of delivering digital clinical trials: lessons learned from a randomised controlled trial of an online behavioural intervention for children and young people.

BACKGROUND: Despite being the gold standard of research to determine effectiveness, randomised controlled trials (RCTs) often struggle with participant recruitment, engagement and retention. These issues may be exacerbated when recruiting vulnerable populations, such as participants with mental health issues. We aimed to update understanding of the scope of these problems in trials of health technology and identify possible solutions through reflecting on experiences from an exemplar trial (Online Remote Behavioural Intervention for Tics; ORBIT). METHOD: We extracted anonymised data on recruitment, retention and requests for more funding and time from trials funded by the largest funder of health technology trials in the UK (the National Institute of Health Research Health Technology Assessment) between 2010 and 2020, and compared these with data from a recent, successful trial (ORBIT). ORBIT aimed to assess the clinical- and cost-effectiveness of blended online and human behavioural therapy for tics in young people. Many of the trial procedures, including recruitment, the intervention and data collection, were undertaken online. RESULTS: Data were extracted on 51 trials conducted between 2010 and 2020. Sixty per cent of trials failed to reach their original recruitment target and only 44% achieved their follow-up in the specified time frame. In contrast, ORBIT recruited to target and achieved 90% follow-up. We posit that these achievements are related to (a) judicious use of digital technology for trial procedures and (b) adequate numbers of highly trained and motivated trial staff. We provide details of both these to help other research teams plan and cost for successful trials. CONCLUSION: An approach combining human and online methods may be advantageous in facilitating trial delivery, particularly in paediatric mental health services. Given the importance of successful clinical trials in advancing healthcare delivery and the waste of human and economic resources associated with unsuccessfully delivered trials, it is imperative that trials are appropriately costed and future research focusses on improving trial design and delivery. TRIAL REGISTRATION: The ORBIT trial is registered with ISRTCN ( ISRCTN70758207 ) Registered on March 20, 2018. and ClinicalTrials.gov ( NCT03483493 ). Registered on March 30, 2018.

Blood pressure, heart rate, and anxiety in schizophrenia.

Anxiety may worsen outcome in psychotic disorders. We assessed anxiety in 44 acutely psychotic subjects and found a positive association with heart rate and blood pressure. Risperidone treatment reduced anxiety but increased heart rate. We concluded that anxiety may adversely affect cardiovascular status in schizophrenia, but the anxiolytic effect of risperidone is not straightforward.

Identification and assembly of V genes as idiotype-specific DNA fusion vaccines in multiple myeloma.

Tumor-specific markers are important in identifying and tracking malignant cells. In this regard, functionally rearranged immunoglobulin variable (V) region genes in B-cell tumors fulfill and extend these criteria. V genes provide signature motifs in tumor cells and can delineate critical features of the clonal history of the cell of origin. They also define a tumor-specific antigen, which can be targeted for immunotherapy. Our focus has been on using novel DNA fusion vaccines to induce antitumor immunity. Here, we describe in detail the methods for identifying tumor-derived V genes at the nucleotide level in the malignant plasma cells of multiple myeloma. We further present the methodology for assembly of tumor V genes as single-chain variable region fragments (scFv), fused in frame with an immunopotentiating nontoxic bacterial sequence, Fragment C (FrC) of tetanus toxin. These scFv.FrC DNA vaccines provide protection in myeloma models and are currently in clinical trials. The vaccines are patient specific and can be rapidly assembled for clinical use.

DIFFERENTIATION OF A PRIMARY CHEMICALLY INDUCED RAT NEPHROBLASTOMA IN ORGAN CULTURE.

The differentiation in organ culture of a rat nephroblastoma is compared with differentiation of normal rat metanephric tissue under the same conditions. The nephroblastoma arose in a 19 week old female Fischer F344 rat given a single intraperitoneal injection of 4.0 µmole methyl(methoxymethy1)nitrosamine (DMN-OMe)/g body weight at one day of age. The tumor consisted almost entirely of spindle cells although a few well-differentiated tubules were scattered throughout the tumor mass. No primitive tubules were seen, but focal aggregates of tumor cells suggestive of nascent epithelial differentiation were frequent. Fragments of the nephroblastoma were cultured on gelfoam sponge in Williams Medium E supplemented with hydrocortisone, insulin, and fetal bovine serum. Within one day extensive tubulogenesis was observed. High mitotic activity resulted in a steady increase in the size of cultured explants over a period of 6 days. By day six, differentiating tubules filled the explant tissue. Cultured fragments were nearly indistinguishable histologically from normal F344 rat fetal kidney explanted to organ culture on day 15 of gestation and grown in vitro for the same period.

A follow-up study of DSM-III-R generalized anxiety disorder with syndromal and subsyndromal major depression.

OBJECTIVE: The authors examined the long-term outcome of generalized anxiety disorder with depressive symptoms utilizing both categorical and dimensional analyses. METHOD: Thirty-nine out-patients with a DSM-III-R diagnosis of generalized anxiety disorder (GAD) with depressive symptoms, both with (n=23) and without (n=16) syndromal major depression (MD) participated in an 11-week clinical trial. Approximately 18 months after initial screening, these individuals were once again evaluated using a structured diagnostic interview and a battery of rating scales. RESULTS: Three distinct groups were discernible at follow-up. Twenty-three (60%) of the patients remained syndromal for GAD; 10 patients (43%) were in partial remission from GAD; six (15%) were asymptomatic. Of the 23 patients who were syndromal for MD at baseline, 13 (56%) remained syndromal for MD at follow-up. All of the patients who were syndromal for MD at follow-up remained syndromal for GAD as well. CONCLUSIONS: Outcomes in this study were quite divergent, though they support the concept of GAD as a chronic illness in most patients, with or without MD. The presence or absence of MD versus subsyndromal depression at baseline appeared to have relatively little impact upon the outcome. Patients with subsyndromal anxiety and depressive symptoms may be at special risk for syndromal disorders over time.

Stability of worry content in GAD patients: a descriptive study.

The stability of worry content was investigated in a sample of 27 individuals diagnosed with Generalized Anxiety Disorder. During an initial evaluation, participants were asked to describe the content of their current worries, and the examining psychiatrist rated the frequency and intensity of these topics. During the following year, the investigators interviewed the participants on a monthly basis assessing the intensity and frequency of original worries, intensity and frequency of new worries, overall worry level, and general anxiety level. Analysis of this longitudinal data indicated level of overall worry and anxiety remained fairly stable over a 12-month period. Although the intensity and frequency of original worries decreased over time, few original worry topics completely remitted. In fact, at the end of the 12-month monitoring period, worry content identified at baseline continued to account for over 65% of the overall worry variance. Most participants did identify new worry topics during the course of the 12-month period, and the frequency and intensity of the new worries were comparable to the decrease in frequency and intensity of the original worries.

Congenital communication of a retroaortic innominate vein with both the left and right atria in the presence of a normal coronary sinus.

We report the first known case of a retro-aortic innominate vein providing continuity between both the left and right atria in the presence of a left superior vena cava and a normal coronary sinus. This unusual structure created a bidirectional shunt with clinical desaturation at baseline and it complicated the management of a 9-year-old patient while undergoing mechanical ventilation. An embryologic mechanism that explains the development of this complex remains elusive.

The therapeutic potential of escitalopram in the treatment of panic disorder.

Panic disorder is a chronic and disabling condition that is often accompanied by other psychiatric and medical conditions. The serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) have been used effectively with panic disorder (PD) and conditions in which panic attacks frequently occur. Escitalopram is the most selective SSRI and a variety of evidence suggests it is of great value in the treatment of panic disorder. In this paper, we review the theoretical and practical implications of its use.