No drugs are currently approved for the treatment of borderline personality disorder (BPD). These studies (a randomised study and its open-label extension) aimed to evaluate the efficacy, safety and tolerability of brexpiprazole for the treatment of BPD.

The Phase 2, multicentre, randomised, double-blind, placebo-controlled, parallel-group study enrolled adult outpatients with BPD. After a 1-week placebo run-in, patients were randomised 1:1 to brexpiprazole 2–3 mg/day (flexible dose) or placebo for 11 weeks. The primary endpoint was change in Zanarini Rating Scale for BPD total score from randomisation (Week 1) to Week 10 (timing of randomisation and endpoint blinded to investigators and patients). The Phase 2/3, multicentre, open-label extension study enrolled patients who completed the randomised study; all patients received brexpiprazole 2–3 mg/day (flexible dose) for 12 weeks. Safety assessments included treatment-emergent adverse events (TEAEs).

Brexpiprazole was not statistically significantly different from placebo on the primary endpoint of the randomised study (N = 324 randomised; N = 110 analysed per treatment group; least squares mean difference −1.02; 95% confidence limits −2.75, 0.70; p = 0.24). Numerical efficacy advantages for brexpiprazole were observed at other time points. The most common TEAE in the randomised study was akathisia (brexpiprazole, 14.0%; placebo, 1.2%); data from the open-label study (N = 199 analysed) suggested that TEAEs were transient.

The primary endpoint of the randomised study was not met. Further research on brexpiprazole in BPD is warranted based on possible efficacy signals at other time points and its safety profile.

ClinicalTrials.gov identifiers: NCT04100096, NCT04186403. Funding: Otsuka, Lundbeck.

To compare time to relapse in patients with major depressive disorder (MDD) stabilised on antidepressant treatment (ADT) + brexpiprazole who were randomised to continued adjunctive brexpiprazole or brexpiprazole withdrawal (switch to placebo).

This Phase 3, multicentre, double-blind, placebo-controlled, parallel-arm, randomised withdrawal study enrolled adults with MDD and inadequate response to 2–3 ADTs. All patients started on adjunctive brexpiprazole 2–3 mg/day (Phase A, 6–8 weeks). Patients whose symptoms stabilised (Phase B, 12 weeks) were randomised 1:1 to adjunctive brexpiprazole or adjunctive placebo (Phase C, 26 weeks). The primary endpoint was time to relapse in Phase C. Depression rating scale score changes were secondary endpoints.

1149 patients were enrolled and 489 patients were randomised (ADT + brexpiprazole n = 240; ADT + placebo n = 249). Median time to relapse was 63 days from randomisation in both treatment groups for patients who received ≥1 dose. Relapse criteria were met by 22.5% of patients (54/240) on ADT + brexpiprazole and 20.6% (51/248) on ADT + placebo (hazard ratio, 1.14; 95% confidence interval, 0.78–1.67; p = 0.51, log-rank test). Depression scale scores improved during Phases A–B and were maintained in Phase C. Mean weight increased by 2.2 kg in Phases A–B and stabilised in Phase C.

Time to relapse was similar between continued adjunctive brexpiprazole and brexpiprazole withdrawal; in both groups, ∼80% of stabilised patients remained relapse free at their last visit. Adjunctive brexpiprazole therapy was generally well tolerated over up to 46 weeks, with minimal adverse effects following brexpiprazole withdrawal.

ClinicalTrials.gov identifier: NCT03538691. Funding: Otsuka, Lundbeck.

The COVID-19 pandemic amplified known challenges associated with the conduct of inpatient clinical trials, while also introducing new ones that needed to be addressed.

Stakeholders based in the United States who participated in the conduct of inpatient therapeutic trials for the treatment of COVID-19 as part of the Accelerating COVID-19 Therapeutic Interventions and Vaccines program identified challenges experienced in the conduct of these trials through a series of meeting to discuss and identify common themes. In addition, innovations developed to address these challenges and other potential solutions that may be utilized in future pandemics were highlighted.

Six thematic challenges including infection control considerations, the interplay between provision of clinical care and research, competing clinical trials, arduous consenting procedures, onerous procedural requirements, and participant recruitment including achieving representation of diverse populations were identified and are discussed here.

Consideration of the lessons learned and recommendation outlined here may allow for more efficient conduct of inpatient clinical trials in future pandemics.

Depression is an independent risk factor for cardiovascular disease (CVD), but it is unknown if successful depression treatment reduces CVD risk.

Using eIMPACT trial data, we examined the effect of modernized collaborative care for depression on indicators of CVD risk. A total of 216 primary care patients with depression and elevated CVD risk were randomized to 12 months of the eIMPACT intervention (internet cognitive-behavioral therapy [CBT], telephonic CBT, and select antidepressant medications) or usual primary care. CVD-relevant health behaviors (self-reported CVD prevention medication adherence, sedentary behavior, and sleep quality) and traditional CVD risk factors (blood pressure and lipid fractions) were assessed over 12 months. Incident CVD events were tracked over four years using a statewide health information exchange.

The intervention group exhibited greater improvement in depressive symptoms (p < 0.01) and sleep quality (p < 0.01) than the usual care group, but there was no intervention effect on systolic blood pressure (p = 0.36), low-density lipoprotein cholesterol (p = 0.38), high-density lipoprotein cholesterol (p = 0.79), triglycerides (p = 0.76), CVD prevention medication adherence (p = 0.64), or sedentary behavior (p = 0.57). There was an intervention effect on diastolic blood pressure that favored the usual care group (p = 0.02). The likelihood of an incident CVD event did not differ between the intervention (13/107, 12.1%) and usual care (9/109, 8.3%) groups (p = 0.39).

Successful depression treatment alone is not sufficient to lower the heightened CVD risk of people with depression. Alternative approaches are needed.

ClinicalTrials.gov Identifier: NCT02458690

Nasal septoplasty is one of the most performed procedures within ENT. Nasal obstruction secondary to a deviated nasal septum is the primary indication for functional septoplasty. Since the coronavirus disease 2019 pandemic, waiting lists have increased and are now long. This study assessed patients on the waiting list for septoplasty and/or inferior turbinate reduction surgery using the Nasal Obstruction Symptom Evaluation instrument.

Patients on our waiting list for septoplasty and/or inferior turbinate reduction surgery were reviewed using a validated patient-reported outcome measure tool to assess symptom severity.

Eighty-six out of a total of 88 patients (98 per cent) had Nasal Obstruction Symptom Evaluation scores of 30 or more. In addition, 78 (89 per cent) and 50 (57 per cent) patients were classified as having ‘severe’ or ‘extreme’ nasal obstruction, respectively. Two patients scored less than 30 and were classified as having non-significant nasal obstruction.

The Nasal Obstruction Symptom Evaluation instrument is a quick and easy way to validate septoplasty waiting lists. In this study, two patients were identified who no longer required surgery.

To investigate the association between pre-trial expectancy, suggestibility, and response to treatment in a trial of escitalopram and investigational drug, COMP360, psilocybin, in the treatment of major depressive disorder (ClinicalTrials.gov registration: NCT03429075).

We used data (n = 55) from our recent double-blind, parallel-group, randomized head-to-head comparison trial of escitalopram and investigational drug, COMP360, psilocybin. Mixed linear models were used to investigate the association between pre-treatment efficacy-related expectations, as well as baseline trait suggestibility and absorption, and therapeutic response to both escitalopram and COMP360 psilocybin.

Patients had significantly higher expectancy for psilocybin relative to escitalopram; however, expectancy for escitalopram was associated with improved therapeutic outcomes to escitalopram, expectancy for psilocybin was not predictive of response to psilocybin. Separately, we found that pre-treatment trait suggestibility was associated with therapeutic response in the psilocybin arm, but not in the escitalopram arm.

Overall, our results suggest that psychedelic therapy may be less vulnerable to expectancy biases than previously suspected. The relationship between baseline trait suggestibility and response to psilocybin therapy implies that highly suggestible individuals may be primed for response to this treatment.

Lewy body dementia (LBD) is a prevalent yet frequently underdiagnosed form of dementia, accounting for up to 15% of all dementia cases.

This study aims to increase awareness and advocacy for LBD by gathering and critically assessing the economic evidence, including the cost of illness and cost-effectiveness of interventions for managing LBD.

A systematic literature review was undertaken with EMBASE, Medline, CINAHL, PsycINFO, NHS Economic Evaluation Database and EconLit. This search was supplemented by grey literature on Google Scholar and reviewing the reference lists of identified studies. The papers included in the review were published between 2008 and 2023, and involved participants with LBD (dementia with Lewy bodies or Parkinson's disease dementia), which either addressed the cost of illness or conducted an economic evaluation.

Thirteen papers were included, comprising ten cost-of-illness studies and three economic evaluations. The cost of LBD tends to be higher than that of other forms of dementia, such as Alzheimer's disease, and these costs escalate more steeply as the disease progresses. These cost differences may not be solely influenced by the subtype of dementia, but possibly also by patient characteristics like physical and cognitive abilities. Cost-effectiveness of potential interventions for LBD is limited.

Despite numerous drug trials and other interventions for dementia, very few have targeted LBD, let alone explored the cost-effectiveness of such therapies for LBD. This disparity highlights the urgent need for cost-effective strategies and interventions targeting LBD. We propose the establishment of universally accepted standards for LBD research.

Despite the intuitive attractiveness of bringing research to participants rather than making them come to central study sites, widespread decentralized enrollment has not been common in clinical trials.

The need for clinical research in the context of the COVID-19 pandemic, along with innovations in technology, led us to use a decentralized trial approach in our Phase 2 COVID-19 trial. We used real-time acquisition and transmission of health-related data using home-based monitoring devices and mobile applications to assess outcomes. This approach not only avoids spreading COVID-19 but it also can support inclusion of participants in more diverse socioeconomic circumstances and in rural settings.

Our team developed and deployed a decentralized trial platform to support patient engagement and adverse event reporting. Clinicians, engineers, and informaticians on our research team developed a Clinical-Trial-in-a-Box tool to optimally collect and analyze data from multiple decentralized platforms.

Applying the decentralized model in Long COVID, using digital health technology and personal devices integrated with our telehealth platform, we share the lessons learned from our work, along with challenges and future possibilities.

Incorporating real-world data using “big data” analysis in healthcare are useful to extract specific information for healthcare delivery system improvement. All-cause mortality is an essential measure to enhance patient safety in clinical trial research, especially for underrepresented pediatric participants.

This study aimed to determine the associations between pediatric mortality and patient-specific factors using the Healthcare Cost and Utilization Project (HCUP) database.

Data from the 2019 the HCUP Kids’ Inpatient Database (KID) were used to conduct a logistic regression analysis to determine associations between pediatric patients’ the chance of survival and their demographic and socioeconomic background, discharge records, and hospital information.

Total number of diagnoses (OR = 0.84), total number of procedures (OR = 0.86), length of stay (OR = 1.04), age intervals greater than 1 year (OR > 1.0), transfer into the hospital from a different acute care (OR = 0.34), major diagnoses of multiple significant trauma (OR = 0.03) or hepatobiliary system and pancreas (OR = 0.10), region of hospital – west and midwest (OR > 1.0), and medium or larger hospital bed size (OR > 1.0) were all significantly associated with the chance of survival for patients participating in pediatric clinical trials (p < 0.05).

Real-world clinical trial data analysis showed the potential improvement area including reallocating trial resources to promote trial quality and safe participation for pediatric patients. Pediatric trials need tools that are developed using user-centered design approaches to satisfy the unique needs and requirements of pediatric patients and their caregivers. Safe intrahospital transfer procedures and active dissemination of successful trial best practices are crucial to trial management, adherence, quality, and safety.

Clinical research provides evidence to underpin and inform advancements in the quality of care, services and treatments. Primary care research enables the general patient population access and opportunities to engage in research studies. Nurses play an integral role in supporting the delivery of primary care research, but there is limited understanding of nurses’ experiences of this role and how they can be supported to facilitate the delivery of research.

To explore the experiences of nurses delivering research studies in primary care settings.

We identified studies published between 2002 and June 2021 from key electronic databases. A two-level inclusion/exclusion and arbitration process was conducted based on study selection criteria. Data extraction and quality appraisal were performed simultaneously. Data were analysed in the form of a narrative synthesis.

The key themes identified included: (1) what nurses value about primary care research and their motivations for study engagement, (2) the role of nurses in research, (3) working with research teams, (4) study training, (5) eligibility screening, data collection and study documentation, (6) nurse/participant dynamic, (7) gatekeeping, (8) relationships with colleagues and impact on recruitment, (9) time constraints and workload demands, and (10) health and safety.

Nurses are integral to the delivery of research studies in primary care settings. The review highlights the importance of good communication by study teams, timely and study-specific training, and support from colleagues to enable nurses to effectively deliver research in primary care.