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ctDNA guided immunotherapy in patients with advanced non-small cell lung cancer: a nationwide Danish, randomised, intervention study (PRELUCA--PRediction in LUng CAncer Treatment) - study protocol

Por: Andersen · M. E. · Nyhus · C. H. · Szejniuk · W. M. · Wahlstrom · S. · Timm · S. · Pallisgaard · N. · Madsen · M. G. · Mikkelsen · M. D. · Ahlborn · L. B. · Gehl · J. · Frank · M. S.
Introduction

PRELUCA is a randomised, intervention, non-inferiority study designed to use real-time, longitudinal circulating tumour DNA (ctDNA) measurements to evaluate the efficacy of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC). The primary outcome is overall survival between the two groups: the standard of care group (computer tomography scan evaluation) and intervention group (ctDNA evaluation).

Methods and analysis

The inclusion and exclusion criteria align with European Society for Medical Oncology treatment guidelines and permit broad inclusion of NSCLC patients, ensuring ‘real-world’ representativeness. The study uses a tumour-informed method, using baseline next generation sequencing analyses to design patient-specific droplet digital PCR assays, which are run with collected blood samples 1 week prior to the intended treatment, enabling real-time evaluation via ctDNA Response Evaluation Criteria in Solid Tumours.

Ethics and dissemination

Inclusion began in July 2023 and patients are now being actively included in five locations across Denmark. Approval by The Committee on Health Research Ethics of Region Zealand was gained on 4 May 2023.

Trial registration number

NCT05889247.

Protective factors for maternal mental health and life satisfaction during the COVID-19 pandemic: a longitudinal analysis

Por: Johannessen · P. M. · Madsen · C. · Hart · R. K. · Lund · I. O. · Pettersen · J. H. · Gustavson · K. · Roysamb · E. · Nesvag · R. · Brandlistuen · R. E. · Ask · H.
Objective

Mothers’ mental health and life satisfaction may have been negatively affected due to challenges during the COVID-19 pandemic. Given the risk of future crises, knowledge of possible mitigating factors in this population is essential. This study aims to examine whether the pandemic affected the level of protective factors such as social support, physical activity and employment situation, and how these factors are associated with mental distress and life satisfaction.

Design

Longitudinal cohort study.

Outcome measures

Primary outcomes were mental distress (measured by the eight-item version of the Hopkins Symptom Checklist) and life satisfaction (measured by the Satisfaction With Life Scale). As the first step, we investigated changes in the levels of social support (defined by the number and frequency of social contact), physical activity (average hours of physical activity during a week), employment situation (actively working vs sick leave or unemployed), alcohol consumption (measured by the Alcohol Use Disorders Identification Test-Consumption) and relationship satisfaction (measured by the five-item version of the Relationship Satisfaction Scale).

Methods

We analysed data from two waves of the Norwegian Mother, Father and Child Cohort Study (n=~18 000 mothers); one pre-pandemic wave and one wave where half of the sample responded after the onset of the pandemic, with pandemic exposure being defined by questionnaire response timing rather than cohort recruitment. To assess changes in protective factors over time and pandemic exposure, we used difference-in-differences analyses and regression discontinuity design. Associations between protective factors with mental distress and life satisfaction, and possible moderation by pandemic exposure, were investigated using multiple regression models with interaction terms adjusted for potential confounders.

Results

Apart from physical activity, which declined less across time in the pandemic group (B=0.09, 99% CI 0.05 to 0.12), protective factors did not change during the pandemic. Social support, employment situation and relationship satisfaction were associated with mental distress and life satisfaction, whereas physical activity showed a unique relationship with mental distress. Most associations were similar across pandemic exposure groups, except employment situation which appeared to have a stronger protective effect in the pandemic group (β=–0.12, 99% CI –0.24 to –0.00).

Conclusions

Changes over time in self-reported levels of protective factors were generally consistent among mothers independent of the pandemic. These factors appear to play an equally important role for mental distress and life satisfaction both under ordinary circumstances and during public health crises. Our findings enhance the understanding of how potential protective factors among mothers are associated with mental distress and life satisfaction in the context of a global stressor. Future studies should investigate additional mitigating factors that may be particularly relevant during global crises and explore the causal relationship between protective factors, mental health and life satisfaction.

Feasibility of micro-costing for hospital-at-home in Danish municipalities: a prospective pilot study

Por: Tayyari · N. · Duvald · I. · Galle Madsen · M. · Engelbrecht Sjol · S. · Nielsen · C. P. · Risor · B. W.
Objectives

To test the feasibility of identifying and quantifying resource use for a Hospital-at-Home (HaH) model in Danish municipalities, we used a micro-costing approach. Additionally, we aimed to generate a transparent activity and time dataset. This dataset will support subsequent tariff development with time-driven activity-based costing and feed into the economic evaluation of an ongoing randomised controlled trial (RCT).

Design

Prospective pilot feasibility study.

Setting

Three municipalities in the Central Denmark Region in collaboration with emergency department specialists and general practitioners.

Participants

56 elderly acute patients treated in HaH during the pilot phase.

Outcome measures

Feasibility of micro-costing data collection (completeness, consistency and acceptability to staff) and descriptive resource-use quantities by activity and provider group. No price assignment or cost estimates are reported.

Results

Patients received a mean of 3.8 HaH treatment days with 7.8 acute team visits and 3.9 municipal-staff visits per treatment course. The acute team spent a mean of 742 min per patient across treatment activities, communication, documentation and transport, while municipal care staff recorded a mean of 213 min. Intravenous medicine administration and vital sign assessments were the most frequent activities. Data completeness and consistency improved over time through co-design and feedback.

Conclusions

Detailed resource-use measurement using provider logs was feasible in a municipal HaH model and produced an activity and time dataset suitable for tariff development. Findings are context-specific and not generalisable due to the small sample. The micro-costing log refined through the pilot will be applied in an RCT, where time and activity data will be used to construct a tariff using time-driven activity-based costing.

If the pain is too much, you go to a hospital: a qualitative study on health-seeking behaviour for human brucellosis in Nakasongola cattle corridor, Uganda

Por: Kulabako · C. T. · Madsen · L.
Objective

Brucellosis ranks fourth among the top seven priority zoonotic diseases for control in Uganda. The effect of individual actions on controlling the spread of infectious diseases in humans and the choices people make regarding symptoms and suspicions must be given a critical role in the management of zoonotic diseases. Understanding the experiences that shape response to brucellosis is crucial if we are to effectively control the spread of brucellosis in the human population. This study aimed to explore people’s experiences and health-seeking behaviour for human brucellosis and elucidate any challenges as perceived by the affected population. This study involved exploring the facilitating factors for seeking healthcare from the perspectives of the affected population and the potential barriers in accessing health services in Nakasongola.

Design

Descriptive qualitative study.

Setting

The study was conducted in the cattle corridor of Nakasongola District within three sub-counties of Nabiswera, Wabinyonyi and Nakitoma, which were purposively selected because of the large herd number (150 cattle per square km and 30–50 cattle per household), high prevalence of brucellosis in humans, thus extensive human–animal interaction, and the community’s susceptibility to brucellosis. Data were collected from November 2023 to January 2024.

Participants

Semi-structured, face-to-face interviews were conducted by the first author with 15 participants for in-depth interviews, who included the people who were recovering/had recovered and their caretakers, and 20 key informants including medical personnel, village health team members and social leaders who were purposively selected.

Analysis

Thematic analysis was conducted to group themes originating in the data into higher-order themes using inductive and deductive approaches.

Results

Key themes were identified in line with literature and the healthcare systems model. The findings highlighted a series of factors that influence and inhibit health-seeking behaviour for human brucellosis. Participants identified the role of sex and religion as some of the social factors, barriers to health information and perceptions of healthcare quality, accessibility and availability of treatment. These insights show the importance of understanding broader social norms and health system constraints to improve timely diagnosis, treatment adherence and overall disease control.

Conclusion

Addressing the factors identified requires a diverse approach that includes improving the quality of health services, promoting health education, challenging societal norms around gender and illness and leveraging the role of religious communities in health promotion. Such efforts could ultimately improve health outcomes in the affected community.

Longitudinal investigation of psychological outcomes associated with screen use in Danish preschool children: study protocol for The Digital Child

Por: Nygaard · M. · Olsen · M. F. · Thomsen · M. M. W. · Hadi · N. H. A. · Trans · K. L. · Horwood · S. · Flensborg-Madsen · T.
Introduction

Despite an increasing use of screens among preschool children and evidence suggesting potential adverse effects, there is a paucity of longitudinal research that aims to disentangle the multifaceted components of screen use and their unique associations with development. We present a protocol for a large-scale national longitudinal study with repeated measurements in Danish preschool children, with the aim of investigating the cross-sectional and cross-lagged longitudinal associations between screen use and psychological outcomes.

Methods and analysis

The Digital Child Study is a national prospective observational cohort of Danish preschool children. Baseline parent-report data collection commenced in 2024 via online questionnaires, and in total will include three time points over 1 year: baseline (age 4 years), and follow-ups at 6 and 12 months (ages 4.5 and 5 years). Participants were divided into two waves based on birth dates, starting in March and September 2024. Recruitment targeted parents and primary caregivers of all Danish children born between specific dates in 2020. Of 30 235 children whose parents were sent invitations, baseline questionnaire data were available for 11 690 (39%).

Children’s screen use was measured by detailed information of amount, content and timing of children’s screen use, and the broader context, incorporating parental mediation strategies, attitudes, motivations and practices. Cognitive and socioemotional developmental outcomes were measured using validated tools such as the Strengths and Difficulties Questionnaire, the Nordic Five-to-Fifteen parent questionnaire and the Behaviour Rating Inventory of Executive Function—Preschool Version. Questionnaire data will be linked to national social and health registries to enable long-term follow-up. Statistical analyses will include longitudinal modelling to explore associations between screen use and developmental outcomes, with sensitivity analyses for robustness. The study’s large sample size provides high statistical power to detect meaningful effects.

Ethics and dissemination

The study adheres to ethical research guidelines, ensuring voluntary participation, confidentiality and compliance with data protection laws, with approvals from relevant authorities. Findings will be disseminated through peer-reviewed publications, conferences and plain-language summaries to engage stakeholders and the broader community.

Effect of nature-based health interventions for individuals diagnosed with anxiety, depression and/or experiencing stress--a systematic review and meta-analysis

Por: Jessen · N. H. · Lovschall · C. · Skejo · S. D. · Madsen · L. S. S. · Corazon · S. S. · Maribo · T. · Poulsen · D. V.
Objectives

The use of natural environments and nature activities as elements in the treatment and rehabilitation of mental health challenges is gaining international attention. The objective of the present review was to summarise the knowledge on the effects of nature-based health interventions (NBHIs) targeting individuals diagnosed with anxiety, depression and/or experiencing stress.

Design

Systematic review and meta-analyses. The quality and certainty of evidence were assessed using the SIGN and GRADE.

Data sources

Searches were performed in Embase, MEDLINE, PsycINFO, CINAHL, Cochrane and Web of Science.

Eligibility criteria

(1) NBHIs, (2) Individuals with a diagnosis of mild to moderate anxiety, depression and/or experiencing stress, (3) Age of participating individuals: 18–84 years, (4) Study designs: randomised controlled trials, cohort studies, case-control studies and case-series studies and (5) Publication date: 2000–2024.

Data extraction and synthesis

Screening, quality appraisal and certainty of evidence, assessed using SIGN and GRADE, were performed by two independent reviewers, except title screening. Meta-analyses were performed using random-effect models.

Results

Nineteen articles were included, of which 14 were included in the meta-analyses. The articles showed substantial variation in design, interventions, settings and risk of bias, limiting the certainty of evidence according to GRADE. Participating in NBHIs led to a small to large effect in mental health with standardised mean changes of –0.80 (95% CI= (–1.56; –0.04)), –0.87 (95% CI= (–1.18; –0.56)), –0.32 (95% CI= (–0.74; 0.09)) and 0.58 (95% CI= (0.39; 0.77)) for anxiety, depression and stress scores and overall mental health scores, respectively.

Conclusions

This is the first systematic review examining the effect of NBHIs exclusively on individuals diagnosed with anxiety, depression and/or experiencing stress. Our findings suggest small to large improvements after participating in NBHIs. However, methodological limitations to the included articles necessitate cautious interpretation.

PROSPERO registration number

CRD42024516270.

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