The number of people living with obesity is increasing rapidly worldwide, and the WHO estimates approximately 5 million deaths yearly from non-communicable diseases related to elevated body mass index (BMI). The most effective treatment for weight loss is bariatric surgery, but due to the associated risks and the need for lifelong care, this is not a viable treatment for every patient. With the advent of gut-hormone-based medications to treat obesity, the effectiveness of non-surgical treatment is approaching that of surgical interventions. We therefore aim to investigate the beneficial and harmful effects of laparoscopic bariatric surgery versus any non-surgical treatment.

We will conduct a systematic review with meta-analysis applying our eight-step procedure to assess thresholds for clinical significance and trial sequential analysis to mitigate the risk of random errors. To identify relevant trials, we will search for both published and unpublished trials, without any language restriction, in major medical databases (CENTRAL, MEDLINE, EMBASE, LILACS, SCI-EXPANDED and CPCI-S) and trial registries. The date range covered by the search is from database inception until final search date—within 3 months prior to submission of final results manuscript. Two review authors will independently screen references, extract data and perform risk-of-bias assessment using the Cochrane Risk of Bias Tool 2 and the Grading of Recommendations, Assessment, Development and Evaluations. We will include randomised clinical trials comparing laparoscopic surgery currently in use with any non-surgical comparator in adults or adolescents with BMI >30 kg/m². Quasi-randomised studies or non-randomised studies will not be included. Our critical outcomes are all-cause mortality, serious adverse events and quality of life, and our important outcomes are major cardiovascular events, weight at follow-up, physical function and glycaemic control. In addition, we have two explorative outcomes: metabolic syndrome or Z-score and reported incident of alcohol abuse or other addictive disorder or self-inflicted harm.

This review will collect and perform secondary analysis of data from publicly available sources and ethical approval is therefore not required. The findings will be published in peer-reviewed journals and presented at relevant scientific conferences. We will strive to publish with open access. Awareness will be made through social media platforms. This review aims to help clinicians in identifying best practices in the wide-spanning field of obesity treatment.

CRD420251135341.

To identify early-occurring healthcare and sociodemographic risk factors associated with lower extremity amputation (LEA) by analysing health trajectories up to 10 years before amputation.

A national, observational, registry-based matched case–control study.

The Danish universal healthcare system, using national health registers.

We included 2551 individuals who underwent first-time LEA in 2017–2018 and matched each to two control groups: (1) The Community Controls Group representing the average population who were matched on age, sex and municipality (n=12 748) and (2) a Diabetes Mellitus/Peripheral Arterial Disease (DM/PAD) Control Group matched on age, sex and DM or PAD duration (n=12 478) representing a high-risk population.

Presence of healthcare, sociodemographic and medication-related risk factors associated with LEA was evaluated across three time periods leading up to amputation: the Immediate (0–2 years prior), Early (2–5 years prior) and Long-term (5–10 years prior) risk period.

Polypharmacy and antibiotic use—particularly dicloxacillin targeting Staphylococcus aureus—were strongly associated with LEA across all time periods. Dicloxacillin was prescribed on average 7.8 years prior to major amputation, with long-term ORs of 2.99 (95% CI 2.51 to 3.56) and 2.07 (95% CI 1.75 to 2.46) compared with community and DM/PAD controls. Opioid and paracetamol use also showed strong associations. Individuals with LEA were more likely to live alone and have lower educational attainment. Frequent dental visits were inversely associated with risk.

This study identifies characteristics associated with LEA, including long-term exposure to dicloxacillin and opioid analgesics, alongside polypharmacy and socioeconomic disadvantage. These factors were detectable up to 10 years before amputation and may serve as early indicators for risk identification and guide targeted general practitioner interventions.

A cancer diagnosis not only profoundly impacts individuals but also the very core of their families, reshaping their lives in many ways. However, there is a lack of focus on the well-being and health of the entire family across adult cancer research. This is concerning given that one-third of the Danish population will get a cancer diagnosis before the age of 75, suggesting that many Danes will become caregivers during their lifetime. In addition, identifying vulnerable families is challenging, and the determinant factors for their vulnerability are unknown.

The principal aim of this study is to investigate family health during cancer treatment. This will be done by gathering information on various parameters such as perceived support, quality of life and self-efficacy in patients with cancer and families across the cancer trajectory. Additionally, the study seeks to pinpoint particularly vulnerable families and investigate contributing factors to their vulnerability.

This mixed-methods study follows a sequential explanatory design, combining patient-reported outcomes in a longitudinal, prospective multicentre survey with interviews conducted with a nested sampling of the participants from the survey. A total of 240 patients diagnosed with prostate-, breast-, gastrointestinal- and lymphoma cancer, and designated adult family caregivers will be recruited from six different sites for the survey. Variables such as family health, needs and perceived support, quality of life, self-efficacy, depression, stress and resilience will be explored. Survey data will be collected at baseline, 3, 6, 12 and 18 months. The interviews (n=12–15) will be conducted twice with patients and caregivers jointly: once during the treatment phase (3 months) and once after completion of treatment (12 months). For the survey part, we estimated a sample size with 90% power and 5% significance to detect a minimal clinically important change in the Family Health Scale. Assuming an SD of 2x22 = 31, based on a cross-sectional SD of 22, 44 patients per group were required; to allow for dropout, 60 per group (240 total) were included. Patient and caregiver characteristics will be summarised descriptively. Longitudinal patient-reported outcomes will be analysed with linear mixed regression, separately for patients and caregivers. Changes will be reported as mean differences with 95% CIs and compared with published minimal clinically important differences or, if unavailable, 0.3xbaseline SD. For the qualitative part, thematic analysis by Braun and Clarke is chosen to extract data, identify patterns and analyse data and themes from the interviews. NVivo will be used for coding interview data.

The study will be conducted in accordance with the Helsinki Declaration. Measures will be taken to ensure confidentiality, data protection and participant safety throughout the study. The results will be published in peer-reviewed journals and conference presentations.

ClinicalTrials.gov: NCT06433349. Protocol version 2.0, June 2024.

Total diet replacements (TDRs) and weight loss medications (WLMs) have proven effective in producing substantial weight loss for individuals with obesity. Evidence is lacking on whether combining these treatments is effective and cost-effective in primary care for adults with obesity class I (body mass index (BMI) 30–34.9) or uncomplicated obesity class II or higher (BMI≥35 without obesity-related disease).

LightCARE is a 2-year 1:1 randomised, parallel-group, clinical superiority trial with blinded outcome assessment evaluating the benefits and harms of an intensive weight loss (IWL) intervention compared with usual care for adults with obesity in Denmark and the UK. The trial will include 400 participants aged 18–60 years with obesity class I or uncomplicated obesity class II or higher. The IWL programme aims to achieve and maintain a weight loss of ≥20% through a flexible and individualised combination of TDR, behavioural support, including physical activity and sleep guidance, and WLM if needed and will continue for 2 years. The control group will receive usual care offered in each country, typically consisting of brief behavioural support for weight loss. The primary outcome is body weight 2 years after randomisation. Secondary outcomes will include the proportion of participants achieving ≥20% weight loss, Short-Form-36 Mental Component Score, 4-m gait speed and Metabolic Syndrome Severity-Z score. Serious adverse events, the incidence of eating disorders and bone mineral density will be evaluated as safety outcomes. We will also examine the cost-effectiveness of the intervention, within the trial and in the longer term through modelling. We will conduct a process evaluation to inform any future implementation.

Ethical approval was granted in Denmark (December 2023, H-23051332) and the UK (August 2024, 24/SC/0210). Findings from the trial will be disseminated through peer-reviewed journals and scientific conferences.

NCT06321432.

The Cardiometabolic function in Offspring, Mother and Placenta after Assisted Reproductive Technology (COMPART) study is a prospective cohort study aiming to explore health outcomes in mothers and children following assisted reproductive technology (ART), with a particular focus on frozen embryo transfer (FET) versus fresh embryo transfer (fresh-ET). The increasing prevalence of ART and FET emphasises the need to assess potential health risks associated with the procedures, both in pregnancy, such as pre-eclampsia and large for gestational age offspring, and in the children, such as obesity and cardiometabolic dysfunction.

The cohort will include 600 pregnant women, their potential partner and their offspring in a 1:1:1 ratio of pregnancies achieved after ART with FET, ART with fresh-ET and women who conceived naturally. The study will involve extensive data collection from electronic medical records; parental questionnaires; biochemical, genetic and epigenetic analyses in blood, urine and placental tissue; and medical imaging (fetal ultrasound and PEA POD scan) and clinical examinations. Outcomes are grouped into six work packages (WPs) related to fetal growth (WP1), pregnancy (WP2), placenta (WP3), offspring (WP4), genetics (WP5) and epigenetics (WP6).

The COMPART study aims to provide valuable insights into the impact of ART and FET on maternal and offspring health and the underlying mechanisms responsible. The study seeks to advance reproductive medicine, shape clinical practice and guidelines and ultimately ensure maternal-fetal health following ART. The study has been approved by the Danish Ethics Committee (H-23071266; February 2024).

NCT06334003

Cortical spreading depolarisation (SD) is a pathological wave of depolarisation in the cortex. SDs occur frequently after severe acute brain injury, and SDs in clusters can contribute to secondary brain damage in patients with severe acute brain injury through hypoperfusion and upregulation of cerebral metabolism in vulnerable brain tissue. Ketamine appears to inhibit SDs both in vitro and in patient series of severe acute brain injury. The KETA-BID trial aims to examine the efficacy and safety of S-ketamine for SDs in severe acute brain injury, as well as the feasibility of the trial design.

This randomised, blinded feasibility and pilot trial includes adults (≥ 18 years) undergoing a supratentorial craniotomy or craniectomy for severe acute brain injury (ie, traumatic brain injury, aneurysmal subarachnoid haemorrhage or spontaneous intracerebral haemorrhage). During surgery, an electrocorticography (ECoG) strip is placed adjacent to injured brain tissue. Patients are continuously monitored throughout their stay at the neurointensive care unit and the neurosurgical step-down unit. In the case of an SD, physiological optimisation of intracranial pressure, brain tissue oxygen tension (PbtO₂), core temperature and blood glucose is initiated. Participants developing SD clusters are randomised for continuous infusion with S-ketamine or matching placebo in a 1:1 allocation with full blinding of the treatment allocation. Infusion rates (ie, dose) and duration of trial medication are adjusted following a dosing algorithm according to SD occurrence. Surviving participants are followed until 6 months after the injury with recording of functional outcome. The primary outcome is occurrence of SDs per hour of monitoring after randomisation.

The Scientific Ethics Committee of the Capital Region of Denmark (H-21056972), the Danish Medicines Agency (EudraCT 2021-003716-12), as well as the Clinical Trials Information System (CTIS 2024-515315-22-00) approved this trial. This trial will provide insight into both SD and the clinical effects of ketamine following severe acute brain injury, presenting a potential new treatment for these patients. The findings will be submitted for publication in peer-reviewed publications.

NCT05095857.