Given that low retention rates are a prevalent challenge in clinical trials, which ultimately affects trial validity, it is recommended that interventions be developed and evaluated to increase trial retention. In the context of trial retention, incorporating behavioural science is endorsed, as it provides a theoretical foundation for considering human behaviour. We hypothesised that an intervention informed by self-determination theory could increase retention in a randomised allergy trial on intralymphatic immunotherapy, as the support of basic psychological needs for autonomy, competence and relatedness is anticipated to lead to more sustained engagement and better outcomes.

To assess the acceptability and feasibility of the intervention and evaluation design, following the complex intervention framework by the Medical Research Council, before proceeding to a randomised evaluation.

A parallel two-arm randomised feasibility study was conducted within the randomised allergy trial.

All participants at one Danish site were eligible for recruitment.

The intervention was a web app informed by self-determination theory to support the basic psychological needs through its thoughtfully designed features. Participants were allocated unblinded across treatment groups to complete daily online questionnaires over a 100-day period from May to August 2022. All participants received a daily text message with a link for the questionnaires. On completion, participants in the control group received a confirmation message, while participants in the intervention group had a browser with the menu of the web app opened for them. The features within the menu were voluntary to use.

The prespecified assessments included evaluating the recruitment rate, retention rate (which reflected both sustained participation and the proportion of completed daily questionnaire entries), the suitability of outcome measures and the acceptability of the intervention and evaluation design to both participants and staff. Qualitative data were collected through a collaborative learning process with participants from the intervention group in November 2022.

A total of 30 participants were invited, randomly assigned 1:1 and analysed, resulting in a recruitment rate of 100%. None were lost to follow-up as all remained in the study for the entire duration. The response rate was 84.5% in the intervention group and 79.1% in the control group, indicating satisfactory retention. Outcome measures were deemed appropriate. No unintended adverse events were identified. The collaborative learning meetings involved three participants in the first meeting and two in the second, comprising a total of five different individuals. Participants found the intervention acceptable. They used it differently but agreed that its components were useful. Technical issues needed fixing, and voluntary free text boxes and registration of medication dosage should be added.

The intervention and evaluation design were assessed as acceptable and feasible. Technical issues were fixed, and additional response options were added before a randomised evaluation.

ILIT.NU: EudraCT 2020-001060-28. ClinicalTrials.gov NCT05191186.

Multimorbidity contributes significantly to poor population health outcomes while straining healthcare systems. Although some multimorbid patients experience an accelerated health decline (a decline in well-being or functional status that cannot be attributed to the natural ageing-related health deterioration), others can remain stable for years. Identifying risk factors for accelerated health decline in persons with multimorbidity could help prevent complications and reduce unnecessary interventions. Our review, therefore, aims to map the evidence on the clinical, biographical and healthcare-related factors associated with an accelerated health decline in multimorbid individuals.

We will use the evidence-mapping review methodology. We will perform a systematic comprehensive literature search in Medline via Pubmed, Cochrane Library, EMBASE, Web of Science and Google Scholar using two broad concepts: ‘multimorbidity’ and ‘longitudinal studies’. We will search with MeSH terms (eg, ‘Multimorbidity’ (Majr), ‘Longitudinal Studies’ (Majr)) and free text words (eg, multimorbidity, multiple chronic condition*, longitudinal), from inception to date of the final search. All original quantitative studies involving participants in primary care and related healthcare settings will be included. Abstract/titles and full-text screening and data extraction will be performed independently by two or more researchers to minimise selection and reporting bias, with conflicts resolved by consensus. The data will be analysed qualitatively, and topics will be extracted to create evidence clusters. Risk factors will be classified in groups and cross-referenced against the outcomes from respective studies into combinations of exposure-outcome clusters. The resulting evidence clusters will be described narratively and presented as bubble plots. The search, initiated in January 2023, will be updated following this protocol review to reflect the most current evidence; exact dates will be reported in the results manuscript.

Due to the nature of the proposed evidence map, ethics approval will not be required. Results from our research will be disseminated through publications in peer-reviewed journals and presentations at local, national and international conferences.

https://osf.io/q72xa/

Combined vascular endothelial growth factor/programmed death-ligand 1 blockade through atezolizumab/bevacizumab (A/B) is the current standard of care in advanced hepatocellular carcinoma (HCC). A/B substantially improved objective response rates compared with tyrosine kinase inhibitor sorafenib; however, a majority of patients will still not respond to A/B. Strong scientific rationale and emerging clinical data suggest that faecal microbiota transfer (FMT) may improve antitumour immune response on PD-(L)1 blockade. Early trials in melanoma with FMT and reinduction of immune checkpoint blockade (ICI) therapy in patients with anti-PD-1-refractory metastatic melanoma were reported in 2021 and demonstrated reinstatement of response to ICI therapy in many patients. Due to anatomical vicinity and the physiological relevance of the gut-liver axis, we hypothesise HCC to be a particularly attractive cancer entity to further assess a potential benefit of FMT in combination with ICI towards increased antitumour immunity. Additionally, HCC often occurs in patients with liver cirrhosis, where liver function is prognostically relevant. There is evidence that FMT may increase hepatic function and therefore could positively affect outcome in this patient population.

This prospective, multicentre, randomised, placebo-controlled, double-blind phase II clinical trial has been designed to assess immunogenicity and safety of FMT via INTESTIFIX 001 combined with A/B in advanced HCC in comparison to A/B with placebo. Primary endpoints are measured as tumour CD8+ T cell infiltration after 2 cycles of treatment with vancomycin, A/B+INTESTIFIX 001 in comparison to vancomycin-placebo, A/B+INTESTIFIX 001-placebo and safety of the therapeutic combination in advanced HCC. INTESTIFIX 001 is an encapsulated FMT preparation by healthy donors with a high alpha-diversity in their gut microbiome for oral administration, manufactured by the Cologne Microbiota Bank (CMB). Sample size was calculated to achieve a specific expected accuracy for the primary immunological endpoint. 48 subjects will be randomised to reach a goal of 42 usable measurements in the modified intention-to-treat set. Subjects will be randomised in a 2:1 ratio to A/B or placebo (28 A/B, 14 placebo).

The study was approved by ethics committee review and the German Federal Ministry of Drugs and Medical Devices. The trial is registered under EU CT no. 2023-506887-15-00. The outcome of the study will be disseminated via peer-reviewed publications and at international conferences.

NCT05690048.

Digital therapeutics (DTx) show promise in bridging mental healthcare gaps. However, treatment selection often relies on availability and trial-and-error, prolonging suffering and increasing costs. Personalised prediction models could help identify individuals benefiting most from specific DTx.

The aim of this secondary analysis was to establish a machine learning-based prediction model for positive treatment outcomes in patients with depressive or anxiety symptoms after 8 weeks of internet-delivered cognitive behavioural therapy (iCBT).

We analysed a large real-world dataset of patients from the online therapy unit iCBT programme in Saskatchewan, Canada (2013–2021). Clinically significant changes in depressive symptoms or anxiety were measured using the Patient Health Questionnaire-9 (PHQ-9) and the Generalised Anxiety Disorder-7 (GAD-7). We trained six prediction models using sociodemographic and mental health-related factors at baseline, compared model performances and calculated Shapley values for feature importance.

Data from 4175 patients using 34 features for prediction, identified by least absolute shrinkage and selection operator regression, showed the Gradient Boosted Model (gbm) and logistic regression (log) performed best, with balanced accuracies of 0.76, 95% CI (0.70 to 0.83) and 0.70, 95% CI (0.63 to 0.77). Shapley values indicated GAD-7 scores at baseline as the most important predictor of clinically significant improvement, along with mental health history and sociodemographic variables.

The gbm and log models achieved comparable accuracy in predicting clinically significant improvement after iCBT, supporting the use of simpler, interpretable methods in clinical practice.

These findings could help improve mental health treatment selection, iCBT assignment, enhance effectiveness and optimise treatment for patients.

NCT05758285.

Chronic low back pain (CLBP) and depressive symptoms (DS) are highly prevalent, burdensome, costly and comorbid health conditions. Osteopathic manipulative treatment (OMT) was shown to improve pain and disability in patients with CLBP; however, the effect on comorbid DS remains less certain. Interestingly, CLBP and DS seem to be associated with changes in interoception, which may be reversed by OMT.

The study protocol proposes a single-blinded, parallel-group, randomised controlled trial to investigate the effect of OMT on clinical symptoms (depression, pain and disability) and interoceptive functions (interoceptive accuracy, sensibility and awareness) in patients with CLBP and comorbid DS. A sample of 60 adult subjects with CLBP and comorbid DS shall be recruited from osteopathic, orthopaedic and physiotherapeutic practices and educational institutes for osteopathy, sports science, psychology and medicine in Hamburg, Germany. Participants will be randomly allocated (1:1 ratio) to receive six 45 min treatment sessions of either OMT (standard-OMT group) or sham treatment imitating OMT (sham-OMT group). Primarily, symptoms of depression, pain and disability will be assessed with the Beck’s Depression Inventory, Second Edition (BDI-II), Numeric Rating Scale (NRS) and Oswestry Disability Index (ODI). Secondarily, interoceptive accuracy, sensibility and awareness will be evaluated using the Heartbeat Tracking Task (HTT), Multidimensional Assessment of Interoceptive Awareness (MAIA-2) and confidence-accuracy correspondence (CAC). Ancillary, the therapeutic alliance will be investigated with the Helping Alliance Questionnaire. Data will be collected at baseline (t₀), the first, third and sixth treatment sessions (t₁, t₃, t₆) and at 3 months follow-up (t₇). The findings will be analysed for between-group differences using descriptive (mean and SD) and inductive statistics (mixed analysis of variance). It is hypothesised that standard-OMT, compared with sham-OMT, will reduce depression, pain and disability (BDI-II, NRS, ODI) and increase interoceptive accuracy, sensibility and awareness (HTT, MAIA-2, CAC) in patients with CLBP and comorbid DS.

The study was approved by the ethics committee of the Medical School Hamburg (MSH-2023/288). The anonymised dataset will be published in an online repository, and the results will be published in peer-reviewed scientific journals.

DRKS00031694.

The recent pandemic caused by SARS-CoV-2 had a profound global impact. While many individuals recovered from COVID-19, some developed long-lasting symptoms that significantly disrupted daily life. The WHO defines this condition as post-COVID-19 condition (PCC). Common symptoms include fatigue, dyspnoea, sleep disturbances and cognitive difficulties. Increasing evidence suggests that PCC is a multifactorial condition, shaped not only by biomedical but also psychological and social factors. This article presents the protocol of the Basel Long COVID Cohort Study (BALCoS), which aims to improve understanding of PCC by capturing clinical, functional and psychosocial aspects through repeated assessments over the course of 1 year.

BALCoS is a prospective, single-site cohort study. Inclusion criteria include either a probable or confirmed history of SARS-CoV-2 infection with persistent symptoms consistent with the WHO definition of PCC, sufficient German language skills and age ≥18 years. At baseline, we collected detailed information on previous SARS-CoV-2 infections, symptom history, reinfections, COVID-19 vaccination status and pre-existing medical conditions. The study includes standardised psychometric assessments, physical performance tests, ecological momentary assessments (EMAs), neurocognitive testing and blood sample collection. Assessments are scheduled at baseline and at 3-month, 6-month and 12-month follow-up. All participants complete psychometric assessments at each time point. Blood samples are only collected at baseline. Neurocognitive testing and physical performance measures are collected at baseline and 12-month follow-up for in-person participants only. Participants who are unable to attend in person complete a remote version of the study, excluding these in-clinic assessments. EMAs are initiated the day after each time point and consist of eight questions over 10 consecutive days. The study is exploratory in nature, with a target sample size of 120 participants. BALCoS is part of the Horizon Europe Long COVID project, a multinational interdisciplinary research consortium integrating mechanistic, clinical and interventional studies.

The study was approved by the Ethics Commission of Northwest and Central Switzerland (BASEC-ID: 2023–00359) and is registered at ClinicalTrials.gov (ID: NCT05781893). All participants provide written informed consent. Study findings will be disseminated through peer-reviewed publications.

NCT05781893.

Trans Tasman Radiation Oncology Group 20.01 CHEST-RT (Chemotherapy and Immunotherapy in Extensive Stage Small cell with Thoracic Radiotherapy) is a single-arm, open-label, prospective, multicentre phase II trial study that aims to establish the safety, feasibility and describe the efficacy of incorporating thoracic radiotherapy (TRT) (concurrent or sequential) to chemotherapy and immunotherapy in patients with extensive-stage small-cell lung cancer.

A single arm of up to 30 evaluable participants given TRT concurrent or sequentially with chemoimmunotherapy will be enrolled. Participants should commence radiotherapy with cycle 3 or cycle 4 of chemotherapy. Those not suitable for concurrent radiotherapy due to large tumour volumes may receive sequential radiotherapy. Accounting for a 15% non-evaluable rate, up to 35 participants will be enrolled. An independent data and safety monitoring committee will review the data and assess safety and feasibility. Progression to a phase III trial would be considered feasible if ≤20% of participants experienced ≥grade 3 oesophageal toxicity and ≤10% experienced ≥grade 3 pneumonitis. This approach would be considered feasible if there is ≤20% treatment discontinuation of systemic therapy secondary to radiation toxicities and ≥75% of participants have tumour volumes that can be safely treated to a dose of 30 Gy in 10 fractions. The primary outcome of the trial is safety and feasibility, and survival and responses will be assessed as secondary endpoints. A predefined subgroup analysis of toxicity will be performed on group 1 (concurrent TRT) versus group 2 participants (consolidation TRT).

This study was approved by the Peter MacCallum Human Research Ethics Committee (HREC/73189/PMCC-2021). The protocol, technical and clinical data will be disseminated by conference presentations and publications. Any modifications to the protocol will be formally documented by administrative letters and will be submitted to the approving HREC for review and approval.

Australian New Zealand Clinical Trials Registry (ACTRN12621000586819) and ClinicalTrials.gov identifier (NCT05796089).

To describe self-reported treatment and exercise strategies among patients with long-lasting low back pain (LBP) 1 month after consultation at a specialised hospital-based Medical Spine Clinic and evaluate their associations with changes in pain and disability 1 and 3 months after consultation.

Prospective cohort study using questionnaire data before consultation (baseline) and 1 and 3 months after consultation.

Specialised hospital-based Medical Spine Clinic, Denmark.

1686 patients with long-lasting LBP completed the baseline questionnaire; 908 patients responded at 1 month, of them 623 responded at 3 month.

Patients were categorised by treatment (physiotherapy, chiropractic treatment, physiotherapy+chiropractic treatment and no recommended treatment) and exercise strategy (exercise continued, exercise ceased, exercise initiated and not exercising).

Pain was assessed by the numeric rating scale (NRS: 0–10), and disability was assessed by the Oswestry disability index (ODI: 0–100).

1-month postconsultation, half of the patients received no recommended treatment; most others received physiotherapy (42%). Nearly half of the patients continued exercise, 28% continued to be inactive, and 22% initiated exercise. For the population as a whole, pain changed by –0.74 (95% CI –0.90; –0.58) and –1.02 (95% CI –1.22; –0.83) points on the NRS at 1- and 3-month follow-up, respectively, and disability by –2.65 (95% CI –3.51; –1.78) and –4.48 (95% CI –5.59; –3.38) points on the ODI. Differences between treatment strategies were small. However, the two groups not exercising improved less compared with those who continued exercise when adjusted for age, sex and baseline level (order of magnitude from 0.07 to 1.18 points on the NRS and from 4.01 to 9.08 points on the ODI). For pain, these group differences were statistically significant at 1 month (p

Mean improvement was negligible, with no differences between treatment strategies. However, patients not exercising showed no or less improvement, highlighting the importance of exercise in managing long-lasting LBP.

Psychosis, characterised by chronic symptoms often emerging in youth, imposes a substantial burden on individuals and healthcare systems. While early detection and intervention can mitigate this burden, there is limited evidence on the cost-effectiveness of such approaches. To address this lack of evidence, this study protocol outlines the health economic implications of an artificial intelligence (AI)-based intervention, the Computer-Assisted Risk-Evaluation (CARE), designed to prevent psychosis. The intervention uses AI technologies to enhance the diagnosis and treatment quality for individuals at high risk of psychosis.

The health economic evaluation has been designed alongside a 12-month multicentre randomised controlled trial comparing CARE with treatment as usual from both payer and societal perspectives. An implementation cost analysis will complement the evaluation, and long-term consequences beyond the trial will be explored descriptively. Based on a literature review, an initial economic logic model will guide subsequent analyses by depicting CARE’s programme theory.

The cost-effectiveness assessment will include averted cases of manifest psychosis and quality-adjusted life-years using the EuroQol 5-Dimensions 3-Level instrument. Other effectiveness outcomes will also be incorporated into a cost–consequence analysis. Cost-effectiveness acceptability curves reflecting statistical uncertainty will be constructed, incorporating various payer and societal willingness-to-pay values. The implementation cost analysis will follow a mixed-methods approach to capture facility-specific costs.

A dark logic model, emphasising negative outcomes, will be developed to investigate long-term consequences. Further, the initial economic logic model will be refined using trial data and expert interviews. This comprehensive approach aims to provide decision-makers not only with evidence on the cost-effectiveness of CARE, but also with a broader understanding of the implications of the intervention.

The study has received ethical approval and plans to disseminate its findings through publication in a peer-reviewed journal and conference presentations.

NCT05813080.

The aim of the study was to analyse patients’ experiences, usability and acceptability of a 12-week self-directed m-health exercise intervention for patients with knee osteoarthritis (OA).

This qualitative study was included in a randomised controlled trial. After completion of a 12-week m-health exercise intervention, 14 structured telephone interviews were conducted in patients with knee OA. The interviews were audio recorded, transcribed and analysed using a combined deductive and inductive content analysis approach.

The study was conducted at a university hospital in southern Germany.

Four themes were identified: (1) facilitators and (2) barriers for (correct) digital exercise participation, (3) ease of use and (4) outcomes. Participants valued ease of use, comprehensibility, flexibility and certain app features (eg, push notifications as reminders, instruction videos, real-time biofeedback) that facilitated guidance, control and motivation to complete exercises. However, some participants requested some kind of human support.

The participants demonstrated predominantly positive experiences and acceptability with the self-directed m-health exercise intervention. As some participants lacked human support, we suggest that the optimal treatment option should be selected according to the preferences and needs of the individual patient.

DRKS00023269.

This study explored the experience of stigma and access to healthcare by persons with long COVID from the majority Dutch and two ethnic minority populations (Turkish and Moroccan) living in the Netherlands.

This was a cross-sectional qualitative study that employed inductive and deductive thematic approaches to data analysis using MAXQDA.

Between October 2022 and January 2023, 23 semi-structured interviews were conducted with participants of Dutch, Moroccan and Turkish ethnic origins with long COVID living in the Netherlands. Participants were men and women aged 30 years and above.

Guided by the concepts of stigma and candidacy, the findings are structured according to the broader themes of stigma and access to care. The findings show that people with long COVID suffer self and public stigma resulting from the debilitating illness and symptoms. Especially among Turkish and Moroccan ethnic minority participants, strong filial obligations and gendered expectations of responsibility and support within their communities further worsen self-stigma. This experience of stigma persisted within healthcare where lack of information and appropriate care pathways led to feelings of frustration and abandonment, especially for participants with pre-existing health conditions which further complicate candidacy. Under the access to healthcare theme, the findings show multiple challenges in accessing healthcare for long COVID due to several multifaceted factors related to the various stages of candidacy which impacted access to care. Particularly for Turkish and Moroccan ethnic minority participants, additional challenges resulting from limited access to information, pre-existing structural challenges and experience of stereotyping based on ethnicity or assumed migrant identity by health professionals further complicate access to health information and long COVID care.

The findings call for urgent attention and research to identify and coordinate healthcare for long COVID. There is also a need for accessible, informative and tailored support systems to facilitate patients’ access to information and care pathways for long COVID. Providing tailored information and support, addressing the various barriers that hinder optimal operating conditions in healthcare and leveraging on social networks is crucial for addressing stigma and facilitating candidacy for persons with long COVID towards improving access to care.

Breast cancer is the most common form of cancer in women. A considerable number of women with breast cancer who have been treated with chemotherapy subsequently develop neurological symptoms such as concentration and memory difficulties (also known as ‘chemobrain’). Currently, there are no validated therapeutic approaches available to treat these symptoms. Cognitive training holds the potential to counteract cognitive impairment. Combining cognitive training with concurrent transcranial direct current stimulation (tDCS) could enhance and maintain the effects of this training, potentially providing a new approach to treat post-chemotherapy subjective cognitive impairment (PCSCI). With this study, we aim to investigate the effects of multi-session tDCS over the left dorsolateral prefrontal cortex in combination with cognitive training on cognition and quality of life in women with PCSCI.

The Neuromod-PCSCI trial is a monocentric, randomised, double-blind, placebo-controlled study. Fifty-two women with PCSCI after breast cancer therapy will receive a 3-week tDCS-assisted cognitive training with anodal tDCS over the left dorsolateral prefrontal cortex (target intervention), compared with cognitive training plus sham tDCS (control intervention). Cognitive training will consist of a letter updating task. Primary outcome will be the performance in an untrained task (n-back task) after training. In addition, feasibility, safety and tolerability, as well as quality of life and performance in additional untrained tasks will be investigated. A follow-up visit will be performed 1 month after intervention to assess possible long-term effects. In an exploratory approach, structural and functional MRI will be acquired before the intervention and at post-intervention to identify possible neural predictors for successful intervention.

Ethical approval was granted by the ethics committee of the University Medicine Greifswald (BB236/20). Results will be available through publications in peer-reviewed journals and presentations at national and international conferences.

ClinicalTrials.gov; NCT04817566, registered on 26 March 2021.

This systematic review investigates the effectiveness of different communication strategies to increase COVID-19 vaccine uptake and willingness.

Systematic review and meta-analysis of randomised controlled trials (RCTs), following recommendations from the Cochrane Handbook and reporting according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline.

We searched the following databases until 27 July 2022: Cochrane COVID-19 Study Register, PsycINFO, CINAHL, Web of Science Core Collection and WHO COVID-19 Global literature.

We included RCTs investigating, any population, communication-based interventions to increase COVID-19 vaccine uptake and comparing these with no intervention (with or without placebo), another communication strategy or another type of intervention.

Screening, data extraction and bias assessment, using the Cochrane ROB 1.0 tool, were conducted by two authors independently. We performed meta-analyses if studies were homogeneous using the Review Manager (RevMan 5) software, synthesised the remaining results narratively and assessed the certainty in the evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach.

We identified 49 studies reporting on the predefined four categories of communication interventions. Evidence from our meta-analyses shows that COVID-19 vaccine uptake may increase when education and information strategies are applied (risk ratio (RR) 1.23, 95% CI 1.17 to 1.28; high-certainty evidence) or social norms are communicated (RR 1.28, 95% CI 1.23 to 1.33; high-certainty evidence) compared with no intervention. The different communication strategies mostly have little to no impact on vaccine intention; however, there may be a slight increase in vaccine confidence when gain framing is applied compared with no intervention.

Overall, we found that education and information-based interventions or social norm-framing strategies are most effective compared with no intervention given. Our findings show that some of the investigated communication strategies might influence policy decision-making, and our results could be useful for future pandemics as well.

PROSPERO (CRD42021296618).