Cardiovascular diseases, overweight, type 2 diabetes and chronic kidney disease increase the risk of cardiovascular events.
Glucagon-like peptide-1 analogues are recommended by the European Society of Cardiology and the American College of Cardiology to lower the risk of death and progression of cardiovascular disease in patients with cardiovascular disease and type 2 diabetes. Semaglutide, tirzepatide and liraglutide are approved by the US Food and Drug Administration and the European Medicines Agency for the treatment of type 2 diabetes mellitus and overweight. CagriSema is currently not approved, but several phase III trials are ongoing.
No previous systematic review has investigated the effects of semaglutide, tirzepatide, CagriSema and liraglutide, which may not be disease-specific, on hard binary outcomes for all trial populations at increased risk of cardiovascular events.
We will conduct a systematic review and search major medical databases (Cochrane Central Register of Controlled Trials, Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, Latin American and Caribbean Health Sciences Literature, Science Citation Index Expanded, Conference Proceedings Citation Index—Science) and clinical trial registries from their inception and onwards to identify relevant randomised trials. We expect to perform the literature search in December 2025. Two review authors will independently extract data and assess the risk of bias. We will include randomised trials assessing the effects of semaglutide, tirzepatide, CagriSema and/or liraglutide in participants with an increased risk of cardiovascular events. The primary outcome will be all-cause mortality. Secondary outcomes will be myocardial infarction, stroke and all-cause hospitalisation. Data will be synthesised by aggregate data meta-analyses, Trial Sequential Analyses and network meta-analysis, risk of bias will be assessed with Cochrane Risk of Bias tool V. 2, and the certainty of the evidence will be assessed by Grading of Recommendations, Assessment, Development and Evaluations and the Confidence in Network Meta-Analysis approach.
This protocol does not present any results. Findings of this systematic review will be published in international peer-reviewed scientific journals.
CRD42024623312.
To evaluate the diagnostic accuracy of CT in identifying small and large bowel obstruction and associated complications, including ischaemia and perforation, in adult patients.
Systematic review and meta-analysis reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy reporting guidelines.
Ovid MEDLINE and Embase were searched from 1946 to 20 February 2025.
The study included randomised controlled trials, cohort studies and case–control studies evaluating the diagnostic accuracy of CT for bowel obstruction in adults (aged ≥18 years). Only studies published in English were included. Conversely, case reports, editorials, conference abstracts without full data and studies focusing exclusively on paediatric populations or animal models were excluded.
Three reviewers independently extracted data on study characteristics, CT modality, diagnostic accuracy metrics (sensitivity, specificity and predictive values) and complications. Risk of bias was assessed using the QUADAS-2 tool. A random-effects meta-analysis was conducted. Heterogeneity was assessed using I² and Tau² statistics.
Sixty-five studies with 9418 patients were included. The pooled sensitivity and specificity of CT for bowel obstruction were 90% (95% CI 78 to 96; I²=56%, Tau²=0.36) and 88.8% (95% CI 78.0 to 94.8; I²=65%, Tau²=0.35), respectively. For bowel ischaemia, CT showed a pooled sensitivity of 47.0% (95% CI 32.4 to 59.9; I²=0%, Tau²=0.00) and specificity of 85.3% (95% CI 77.9 to 89.5; I²=1%, Tau²=0.45). Multidetector CT (MDCT) outperformed older modalities across all endpoints. Ischaemia was present in 22.05% of all cases, with higher rates in small bowel obstruction. Perforation and mortality rates were 3.98% and 4.40%, respectively. No significant publication bias was detected, and the certainty of evidence was graded as moderate for most diagnostic accuracy outcomes.
CT, particularly MDCT, offers high diagnostic accuracy for bowel obstruction and is a critical tool for detecting serious complications such as ischaemia and perforation. However, sensitivity for ischaemia remains modest. Standardised protocols and prospective studies are needed to enhance early identification and optimise care pathways.
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.
by Jakob Morén, Barbro Persson, Anna Sörman, Åke Lundkvist, Hanin Shihab, Marie Studahl, Malin Veje, Göran Günther, Gabriel Westman
BackgroundTick-borne encephalitis is a viral infection of the central nervous system that may cause severe illness and long-term sequelae, to which underlying mechanisms are not completely understood. Autoantibodies against the N-methyl-D-aspartate receptor (anti-NMDAR) may be triggered by immunologic events, occur sporadically, and can cause autoimmune encephalitis. Following herpes simplex encephalitis and Japanese encephalitis, anti-NMDAR autoantibodies may develop and have been associated with relapse or impaired cognitive recovery. Tick-borne encephalitis has been shown to trigger anti-NMDAR encephalitis in sporadic cases, but the frequency of autoimmunization is unknown.
ObjectivesThe objective of this study was to assess the frequency of intrathecal anti-NMDAR antibody development following tick-borne encephalitis and to explore whether such antibodies could be relevant to cognitive complaints.
MethodsAdult patients with tick-borne encephalitis were included retrospectively from one cohort and prospectively from another. A stored post-acute cerebrospinal fluid sample was required for anti-NMDAR analysis. Two commercial kits (Euroimmun AG, Lübeck, Germany) were used to detect anti-NMDAR IgG antibodies in cerebrospinal fluid.
ResultsA total of 71 cerebrospinal fluid samples from 53 patients were analyzed for anti-NMDAR antibodies. Samples were obtained at a median of 91 days (range 21–471) after onset of central nervous system symptoms. Anti-NMDAR antibodies were detected in two samples from a single tick-borne encephalitis patient, corresponding to 1.9% of patients (95% CI: 0.05–10.1%).
ConclusionsThe development of intrathecal anti-NMDAR autoantibodies following tick-borne encephalitis is a rare event, and further studies are needed to clarify their potential relevance to cognitive outcomes in a minority of cases. Testing for anti-NMDAR antibodies in cerebrospinal fluid may be considered in patients who experience clinical deterioration following an initial recovery.
Health systems’ (HS) adaptations to climate change (CC) cover two major, and interrelated dimensions: (1) Environmental sustainability—actions aimed at limiting the negative impact of HS on the environment (eg, by reducing greenhouse gas emissions) and (2) Climate resilience—adaptations focused on improving HS’ ability to cope with the impact of CC (eg, by improving HS preparedness to climate-induced natural disasters). Within both dimensions, a diversity of actions, at different HS levels, can take place. The general objective is to provide health policy makers with a comprehensive evidence-based set of recommendations on the scope and effectiveness of HS adaptations to CC.
An umbrella review will be conducted. Systematic reviews will be included if: (1) They focus on HS adaptations to CC (including both environmental sustainability and climate resilience strategies/actions), (2) Were published since 2015 and (3) Report a quality appraisal of included studies. Five databases were searched: (1) MEDLINE via PubMed, (2) Scopus, (3) Web of science core collection, (4) ProQuest Central and (5) The Cochrane Database of Systematic Reviews. Two reviewers will independently assess studies’ eligibility, conduct quality appraisal and perform data extraction. Data will be synthesised using both quantitative and qualitative methods. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses will guide the reporting of results.
Ethical approval is not required, as this study involves the collection and analysis of secondary data only. The results will be submitted for publication in a peer-reviewed journal and disseminated via dedicated research channels and social media platforms.
CRD420251052647.
Parkinson’s disease is a neurological disease with a rising incidence and prevalence. Patients with Parkinson’s disease may receive antipsychotics, for example, due to Parkinson’s disease psychosis. Parkinson’s disease psychosis is characterised by visual hallucinations and other psychotic symptoms. To date, no systematic review has evaluated the effects of antipsychotics in patients with Parkinson’s disease. Therefore, this review aims to assess the beneficial and harmful effects of antipsychotics for Parkinson’s disease.
This is a protocol for a systematic review. A search specialist will perform a search in major medical databases (eg, MEDLINE (Medical Literature Analysis and Retrieval System Online), EMBASE (Excerpta Medica database), CENTRAL (Cochrane Central Register of Controlled Trials)) and clinical trial registries. Published and unpublished randomised clinical trials comparing antipsychotics to any control (placebo, standard care or other antipsychotics) in patients with Parkinson’s disease will be included. Two review authors will independently extract data and conduct risk of bias assessments with the Cochrane Risk of Bias tool—V.2. Primary outcomes will be all-cause mortality, serious adverse events and significant falls. Secondary outcomes will be hospitalisations, non-serious adverse events, Unified Parkinson’s Disease Rating Scale total score and psychotic symptoms using any valid symptom scale. Data will be synthesised by aggregate meta-analysis, trial sequential analysis and network meta-analysis. Several subgroup analyses are planned. An eight-step procedure will be used to assess if the thresholds for clinical significance are crossed, and the certainty of the evidence will be assessed by GRADE (Grading of Recommendations Assessment, Development and Evaluations) and CiNeMA (Confidence in Network Meta-Analysis) approach.
This protocol does not include results, and ethics approval is not required for the project. The findings from the systematic review will be published in international peer-reviewed scientific journals.
PROSPERO ID: CRD42025633985. Available from https://www.crd.york.ac.uk/PROSPERO/view/CRD42025633985.
To increase the sustainability of healthcare, clinical trials must assess the environmental impact of interventions alongside clinical outcomes. This should be guided by Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) and Consolidated Standards of Reporting Trials (CONSORT) extensions, which will be developed by The Implementing Climate and Environmental Outcomes in Trials Group. The objective of the scoping review is to describe the existing methods for reporting and measuring environmental outcomes in randomised trials. The results will be used to inform the future development of the SPIRIT and CONSORT extensions on environmental outcomes (SPIRIT-ICE and CONSORT-ICE).
This protocol outlines the methodology for a scoping review, which will be conducted in two distinct sections: (1) identifying any existing guidelines, reviews or methodological studies describing environmental impacts of interventions and (2) identifying how environmental outcomes are reported in randomised trial protocols and trial results. A search specialist will search major medical databases, reference lists of trial publications and clinical trial registries to identify relevant publications. Data from the included studies will be extracted independently by two review authors. Based on the results, a preliminary list of items for the SPIRIT and CONSORT extensions will be developed.
This study does not include any human participants, and ethics approval is not required according to the Declaration of Helsinki. The findings from the scoping review will be published in international peer-reviewed journals, and the findings will be used to inform the design of a Delphi survey of relevant stakeholders.
Registered with Open Science 28 of February 2025.
The aim of this study was to analyse associations between crowded housing and children’s indoor living environment, respiratory and allergic disorders and general health.
A cross-sectional study.
Sweden, using data from the Swedish National Environmental Health Survey 2019.
The study sample included 48 512 children (aged 6–10 months, 4 years and 12 years). We also investigated associations in vulnerable subgroups, such as children with asthma and those living under unfavourable socioeconomic conditions.
Primary outcomes in the living environment were at least one sign of mould, poor indoor air quality, unpleasant odours, too warm indoors in summer and too cold indoors in winter. Primary outcomes for children’s health were asthma, airway problems, breathing difficulties, rhinitis symptoms, mould and mites allergy, pollen allergy, furred pet allergy and good general health.
About one in five children lived in an overcrowded home. Factors from the indoor living environment such as perceived poor indoor air quality and mould were significantly associated with crowded housing. Moreover, children who lived in overcrowded conditions were less likely to report good general health than children in non-crowded households (OR 0.64, 95% CI 0.54 to 0.76). This association was even stronger in children with asthma (OR 0.51, 95% CI 0.34 to 0.77). Few significant associations were, however, observed with the respiratory and allergic health outcomes.
Crowded housing is associated both with a poor indoor environment and with poorer general health in children. Children with asthma may experience even poorer general health.
Incretin-based drugs, including glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RAs, are increasingly used in the management of type 2 diabetes mellitus and obesity. While these agents have shown cardiovascular benefits, their effects on both cardiovascular outcomes and cardiac structure and function remain uncertain—particularly in patients with and without a history of heart failure (HF).
We will conduct a systematic review and search major medical databases (Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica Database (EMBASE), Latin American and Caribbean Health Sciences Literature (LILACS), Science Citation Index Expanded (SCI-EXPANDED) and Conference Proceedings Citation Index-Science (CPCI-S)), as well as clinical trial registries from their inception and onwards to identify relevant randomised trials. The literature search is scheduled for July 2025. Two review authors will independently extract data and assess risk of bias. We will include randomised controlled trials assessing the effects of cagrilintide/semaglutide, liraglutide, semaglutide and tirzepatide in patients with and without a history of HF. The primary outcome will be cardiovascular mortality. Secondary outcomes will include HF hospitalisation, myocardial infarction, stroke, heart rate, systolic blood pressure, N-terminal pro B-type natriuretic peptide, left ventricular ejection fraction, left ventricular end-diastolic volume and left ventricular end-systolic volume. Data will be synthesised by aggregate data meta-analyses and trial sequential analysis. Risk of bias will be assessed with the Cochrane Risk of Bias tool, version 2, and the certainty of the evidence will be assessed by Grading of Recommendations, Assessment, Development and Evaluations (GRADE).
As this study is a systematic review based on secondary analysis of published data, ethical approval is not required. Findings will be published in international peer-reviewed scientific journals.
CRD420251003374.
The evidence for the optimal duration of psychotherapy for borderline personality disorder (BPD) is scarce. Two previous trials have compared different durations of psychotherapy. The first compared 6 months versus 12 months of dialectical behaviour therapy for BPD (the FASTER trial). The second compared 5 months versus 14 months of mentalisation-based therapy for BPD (the MBT-RCT trial). The primary objective of the present study will be to provide an individual patient data pooled analysis of two randomised clinical trials by combining the two short-term groups and the two long-term groups from the FASTER and MBT-RCT trials, thereby providing greater statistical power than the individual trials. Accordingly, we will evaluate the overall evidence on the effects of short-term versus long-term psychotherapy for BPD and investigate whether certain subgroups might benefit from short-term versus long-term psychotherapy.
An individual patient data pooled analysis of the FASTER trial and the MBT-RCT trial will be conducted. The primary outcome will be a composite of the proportion of participants with a suicide, a suicide attempt or a psychiatric hospitalisation. The secondary outcome will be the proportion of participants with self-harm. Exploratory outcomes will be BPD symptoms, symptom distress, level of functioning and quality of life. We will primarily assess outcomes at 15 months after randomisation for the FASTER trial and at 16 months after randomisation for the MBT-RCT trial. Predefined subgroups based on the design variables in the original trials will be tested for interaction with the intervention as follows: trial, sex (male compared with female), age (below or at 30 years compared with above 30 years) and baseline level of functioning (Global Assessment of Functioning baseline score at 0–49 compared with 50–100).
The statistical analyses will be performed on anonymised trial data that have already been approved by the respective ethical committees that originally assessed the included trials. The final analysis will be published in a peer-reviewed scientific journal and the results will be presented at national seminars and international conferences.
CRD42024612840.
In this case study conducted in a Danish general practice, we aimed to explore how patients with obesity experience a novel treatment approach: group consultations (GCs) for weight loss, lifestyle changes and semaglutide treatment. To receive semaglutide treatment, patients were required to participate in GCs focused on lifestyle changes.
A qualitative study design comprising individual, semistructured interviews was used. Patients were asked to reflect on and describe their past experiences with participating in GCs. Thematic analysis was used as an analytical strategy.
A general practice located in a larger city in the Region of Southern Denmark.
12 patients (eight women and four men) with obesity, aged between 27 years and 69 years, who met the Danish obesity treatment criteria for semaglutide (body mass index over 30 kg/m2 or over 27 kg/m2 with comorbidities), were included. Data were collected from 1 November 2023 to 31 January 2024.
Before attending GCs, patients were worried about sharing personal information with other patients and losing their confidentiality. They also feared being judged by the others in the group, possibly due to previous experiences of stigmatisation. However, after participating in GCs, patients reported positive experiences with peer sharing, had no issues with confidentiality and found the consultations beneficial. Most patients indicated a preference for GCs over one-on-one consultations in the future.
Despite initial concerns about confidentiality and stigmatisation, patients ultimately had positive experiences and gained valuable peer support during group GCs in general practice. Various aspects of the group design, such as the hybrid consultation format and the role of the facilitator, may impact the effectiveness of peer support and influence patients’ overall experience of GCs.
Distal radius fractures account for one-fifth of all fractures in the active elderly population and may cause chronic pain, loss of hand function and reduced work productivity, imposing a significant socioeconomic burden. Most are initially treated with closed reduction and casting, but 30% subsequently require surgery due to insufficient realignment. The current approaches for analgesia for closed reduction are suboptimal. A brachial plexus nerve block provides complete pain relief and muscle relaxation distal to the elbow, potentially creating better conditions for realignment of the fractured bone ends. This may ultimately translate into reduced need for surgery and result in better functional outcomes and fewer complications compared to a haematoma block, which is the current standard care in Denmark.
The BLOCK Trial is an investigator-initiated, parallel-group, allocation-concealed, outcome assessor and analyst-blinded, superiority, randomised, controlled, clinical multicentre trial performed at 11 Danish emergency departments. Eligible adult patients with a distal radius fracture who need closed reduction will be included and allocated 1:1 to either an ultrasound-guided brachial plexus nerve block or a haematoma block. The primary outcome is the proportion of patients with distal radius fracture surgery 90 days after closed reduction. We will include 1716 participants to detect or discard a relative risk reduction of surgery of 20%. Secondary outcomes include treatment-related complications, patient-reported wrist function, pain during closed reduction and proportion of patients with unacceptable radiographic fracture position immediately after closed reduction.
The trial is approved by the Danish Medicines Agency and the Danish Research Ethics Committees (EU CT number: 2024-512191-35-00). All results will be summarised on www.theblocktrial.com, clinicaltrials.gov and euclinicaltrials.eu after publication. Primary and secondary outcome results from 0 to 90 days will be presented in the main article and submitted to a peer-reviewed journal. Results from outcomes on the 12-month follow-up will be presented separately.
(1) To codesign a health literacy intervention within a specialist healthcare setting to help the parents of children with epilepsy access, comprehend, use and communicate information and (2) to assess the intervention's feasibility by exploring stakeholders' perspectives on its usefulness, ease of use of trial methods and contextual factors impacting its execution.
A codesign participatory approach followed by a feasibility approach inspired by the OPtimising HEalth LIteracy and Access to Health Services (Ophelia) process for health literacy intervention development.
(1) The codesign approach included workshops with (a) multidisciplinary personnel (n = 9) and (b) parents (n = 12), along with (c) an interview with one regional epilepsy specialist nurse (n = 1). The participants discussed parents' health literacy needs on the basis of vignettes and brainstormed service improvements. A three-step intervention was subsequently designed. (2) The intervention's feasibility was assessed via interviews with six parents (n = 6), a focus group interview with study nurses, a short doctors survey and a log of time spent testing the intervention.
(1) The parents of first-time admitted children to a specialist epilepsy hospital were targeted for the intervention. Nurse–parent consultations were central to the intervention, activating parents in codeveloping and executing a tailored education plan. (2) Feasibility: parents (n = 6) experienced consultations and education plans that were beneficial for enhancing their self-efficacy in managing the child's condition. The study nurses (n = 3) acknowledged positive outcomes in streamlining patient education but felt that their training on the intervention methods was insufficient. Both parents and nurses identified limited personnel resources as a significant barrier to executing the intervention.
The codesigned intervention engaged nurses and parents in HL development despite system barriers. The parents experience enhanced self-efficacy in managing their child's condition. However, needs refinements and further feasibility tests are needed before future implementation.
The Consort Statement 2010 extension for reporting non-randomised pilot and feasibility studies was used to ensure the methodological quality of the study. A Consort Statement 2010 checklist is provided as an additional file.
The collaboration of parents within the target group, the providers involved and the project's steering committee was crucial in codesigning and evaluating this three-step intervention. Parents and multidisciplinary providers actively contributed through workshops, interviews and in discussion meetings. The study nurses testing the intervention played a key role in defining the documentation process for the codeveloped education plan.
This three-step health literacy intervention can positively impact parents' self-efficacy in managing their child's condition. Enhancing nurses' communication skills is essential for improving parents' health literacy, making it crucial to allocate resources for such training. The intervention content and strategies to meet parents' health literacy needs require refinement, with more provider involvement to better adapt it to the context. Future studies should focus on further feasibility testing by considering a more flexible time frame.
Open Science Framework: https://osf.io/fg9c7/
To determine patients', nurses' and researchers' opinions on the appropriateness and completeness of the proposed conceptualization of nurses' support of hospitalised patients' self-management.
A modified Delphi study.
We conducted a two-round Delphi survey. The panel group consisted of patients, nurses and researchers. The conceptualization of nurses' support of hospitalised patients' self-management presented in the first Delphi round was based on previous research, including a scoping review of the literature. Data was analysed between both rounds and after the second round. Results are reported in accordance with the guidance on Conducting and Reporting Delphi Studies (CREDES).
In the first round all activities of the proposed conceptualization were considered appropriate to support the patients' self-management. Panel members' comments led to the textual adjustment of 19 activities, the development of 15 new activities, and three general questions related to self-management support during hospitalisation. In the second round the modified and the newly added activities were also deemed appropriate. The clarification statements raised in the first Delphi round were accepted, although questions remained about the wording of the activities and about what is and what is not self-management support.
After textual adjustments and the addition of some activities, the proposed conceptualization of nurses' support in patients' self-management while hospitalised have been considered appropriate and complete. Nevertheless, questions about the scope of this concept still remains. The results provide a starting point for further discussion and the development of self-management programs aimed at the hospitalised patient.
The results can be considered as a starting point for practice to discuss the concept of nurses' support for hospitalised patients' self-management and develop, implement and research self-management programs specific for their patient population.
Results are reported in accordance with the guidance on Conducting and Reporting Delphi Studies (CREDES).
Patients were involved as expert panellist in this Delphi study.
Self-management support during hospitalisation is understudied, which undermines the development of evidence-based interventions.
A panel, consisting of patients, nurses and researchers, agreed on the appropriateness of a conceptualization of nurses' support of inpatients' self-management, and identified some points for discussion, mainly related to the boundaries of the concept self-management.
This study is crucial for generating conceptual understanding of how nurses support patients' self-management during hospitalisation. This is necessary for policy, clinical practice, education, and research on this topic.