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Abstract Background Today, the prognostic tools available at the time of diagnosis in colorectal cancer (CRC) are limited. Better prognostic tools are a prerequisite for personalised treatment. This study aimed to investigate whether circulating tumour DNA (ctDNA) markers found in plasma before clinical diagnosis of CRC could contribute to the prediction of poor prognosis. Methods This observational cohort study included patients diagnosed with CRC stage I-III within 24 months following participation in the Trøndelag Health Study (n = 85). Known methylated ctDNA biomarkers of CRC were analysed by PCR in plasma. Outcomes were overall survival (OS), recurrence-free survival (RFS) and poor prognosis (PP). Candidate clinical and methylated ctDNA predictors of the outcomes were identified by Cox regression analyses. Results Methylated GRIA4 (HR 1.96 (1.06–3.63)), RARB (HR 9.48 (3.00–30.00)), SLC8A1 (HR 1.97 (1.03–3.77)), VIM (HR 2.95 (1.22–7.14)) and WNT5A (HR 5.83 (2.33–14.56)) were independent predictors of OS, methylated RARB (HR 9.67 (2.54–36.81)), SDC2 (HR 3.38 (1.07–10.66)), SLC8A1 (HR 2.93 (1.01–8.51)) and WNT5A (HR 6.95 (1.81–26.68)) were independent predictors of RFS and methylated RARB (HR 6.11 (1.69–22.18)), SDC2 (HR 2.79 (1.20–6.49)) and WNT5A (HR 5.57 (3.04–15.26)) were independent predictors of PP (p

Abstract Background This retrospective study analyzed the incidence of subsequent brain metastases after palliative radiotherapy or chemoradiation in patients with stage II/III non-small cell lung cancer (NSCLC). Risk factors for brain metastases development and survival after diagnosis were evaluated. Methods Different baseline parameters including but not limited to age, stage and target volume size were assessed. Outcomes were abstracted from electronic health records. Uni- and multivariate tests were performed. Results The study included 102 patients and found an actuarial risk of brain metastases of 15% (standard error ± 4) at one year and 20% (± 5) at two years. The maximum time interval was 15 months from start of radiation treatment. A non-significant survival difference was observed (median 12 months without versus 8.3 months with brain metastases, p = 0.21). Incidence was higher in patients with N2/3 stage, larger planning target volume size, and younger age (univariately significant factors). Trends were seen for stage III and adenocarcinoma histology. The multivariate analysis confirmed age as the most important risk factor. Conclusion The risk of brain metastases development was comparable to that reported in studies of curative chemoradiation. All events occurred within 15 months of follow-up, suggesting that long-term surveillance imaging may not be warranted. Patients younger than 60 years had a very high risk of brain metastases development.

Abstract Background Individuals with non-celiac gluten/wheat sensitivity (NCGWS) experience improvement in gastrointestinal symptoms following a gluten-free diet. Although previous results have indicated that fructo-oligosaccharides (FOS), a type of short-chain fructans, were more likely to induce symptoms than gluten in self-reported NCGWS patients, the underlying mechanisms are unresolved. Methods Our main objective was therefore to investigate whether FOS-fructans and gluten affect the composition and diversity of the faecal microbiota (16S rRNA gene sequencing), faecal metabolites of microbial fermentation (short-chain fatty acids [SCFA]; gas chromatography with flame ionization detector), and a faecal biomarker of gut inflammation (neutrophil gelatinase-associated lipocalin, also known as lipocalin 2, NGAL/LCN2; ELISA). In the randomised double-blind placebo-controlled crossover study, 59 participants with self-reported NCGWS underwent three different 7-day diet challenges with gluten (5.7 g/day), FOS-fructans (2.1 g/day), and placebo separately (three periods, six challenge sequences). Results The relative abundances of certain bacterial taxa were affected differently by the diet challenges. After the FOS-fructan challenge, Fusicatenibacter increased, while Eubacterium (E.) coprostanoligenes group, Anaerotruncus, and unknown Ruminococcaceae genera decreased. The gluten challenge was primarily characterized by increased abundance of Eubacterium xylanophilum group. However, no differences were found for bacterial diversity (α-diversity), overall bacterial community structure (β-diversity), faecal metabolites (SCFA), or NGAL/LCN2. Furthermore, gastrointestinal symptoms in response to FOS-fructans were generally not linked to substantial shifts in the gut bacterial community. However, the reduction in E. coprostanoligenes group following the FOS-fructan challenge was associated with increased gastrointestinal pain. Finally, correlation analysis revealed that changes in gastrointestinal symptoms following the FOS-fructan and gluten challenges were linked to varying bacterial abundances at baseline. Conclusions In conclusion, while FOS-fructans induced more gastrointestinal symptoms than gluten in the NCGWS patients, we did not find that substantial shifts in the composition nor function of the faecal microbiota could explain these differences in the current study. However, our results indicate that individual variations in baseline bacterial composition/function may influence the gastrointestinal symptom response to both FOS-fructans and gluten. Additionally, the change in E. coprostanoligenes group, which was associated with increased symptoms, implies that attention should be given to these bacteria in future trials investigating the impact of dietary treatments on gastrointestinal symptoms. Trial registration Clinicaltrials.gov as NCT02464150.

Abstract Illness trajectories in people with first-episode psychosis (FEP) vary significantly over time. Identifying early-course parameters predicting outcomes is essential, but long-term data still needs to be provided. We conducted a 10-year follow-up study of a comprehensive first-episode psychosis (FEP) cohort investigating the prevalence of clinical recovery (CR) and treatment resistance (TR) after ten years, as well as clinical, demographic, and pre-illness predictors of long-term outcomes. 102 participants with FEP DSM-IV Schizophrenia spectrum disorders were recruited within their first year of treatment. The Treatment Response and Resistance in Psychosis Working Group (TRRIP) and the Remission in Schizophrenia Working Group (RSWG) criteria were used to define TR and CR, respectively. At 10-year follow-up, 29 (29%) of the participants were classified as in CR, while 32 (31%) were classified as TR. We also identified a larger middle group (n = 41, 40%) consisting of participants in partial recovery. 7% of all participants had tried Clozapine at the 10-year follow-up. Logistic regression analyses identified insidious onset (OR = 4.16) and baseline disorganized symptoms (OR = 2.96) as significantly associated with an increased risk of developing TR. Good premorbid academic adjustment (OR = 1.60) and acute onset (OR = 3.40) were associated with an increased chance of CR. We identified three long-term outcome groups by using recent consensus definitions. We also identified the potential importance of assessing baseline disorganized symptoms and monitoring patients with insidious onset more closely. Further, the findings suggest that clinicians should pay close attention to early-course parameters and provide adequate treatment to improve long-term outcomes of FEP.

Abstract Background Worldwide, peers support has been shown to play a crucial role in supporting people with mental illness in their personal recovery process and return to everyday life. Qualitiative studies underpinning the mechanisms of change in peer support has been reviewed. However, the findings are primeraly based on the perspectives of peer support workers employed in mental health services. Thus, qualitiative studies elucidating the mechanisms of change from the recipient perspective in mental health service independent civil society settings are higly needed to further contribute to the evidence of peer support. The ‘Paths to every day life’ (PEER) is evaluated in a randomized trial and is substantiated by qualitative studies investigating the experiences of PEER from the perspectives of the recipients and the facilitators of peer support. The purpose of this qualitative study underpinned by critical realism was to substantiate the PEER intervention program theory by gaining deeper insight into the change mechanisms and elaborate how, when, and under what circumstances the peer support groups potentially had or did not have an impact on personal recovery from the perspectives of the recipients of peer support. Methods Eleven individuals were interviewed at the end of the ten-week group course. The semi-structured realist-inspired interviews were audio recorded and transcribed verbatim. The analysis was guided by reflective thematic analysis and through an abductive framework based on the program theory. Data were coded and analysed in Nvivo software. Results Four overarching themes were identified that informed and nuanced the program theory: 1) Connectedness as a prerequisite for engagement; 2) A sense of hope by working out new paths to recovery; 3) Seeing new sides of oneself; and 4) Sprout for change. Conclusions This study substantiates the program theory and the quantitative results of the PEER trial by elaborating on mechanisms that were felt to be essential for the personal recovery process from the perspectives of the recipients of the group-based peer support. In addition, the study points out that the opportunities to act in everyday life depended on individual context and where the group participants were on their recovery journey. Trial registration ClinicalTrials.gov identifier: NCT04639167.

Abstract Cambodia’s goal to eliminate malaria by 2025 is challenged by persistent transmission in forest and forest fringe areas, where people are exposed to Anopheles mosquito bites during the day and night. Volatile pyrethroid spatial repellents (VPSRs) and insecticide-treated clothing (ITC) could address these gaps. This study evaluated the outdoor application of one passive transfluthrin-based VPSR, four etofenprox-ITCs paired with a picaridin topical repellent, and a combination of VPSR and ITC against wild Anopheles landing in Cambodia. A 7 × 7 Latin-square study was conducted over 49 collection nights in temporary open structures in Mondulkiri Province. All interventions substantially reduced Anopheles landing, with protective efficacy ranging from 61 to 95%. Mathematical modeling showed significant reductions in vectoral capacity, especially with the combined ITC and VPSR and VPSR alone, albeit with decreased effectiveness over time. These interventions have the potential to reduce outdoor and daytime Anopheles biting, offering valuable contributions to malaria elimination efforts in Cambodia and the Greater Mekong Subregion, contingent upon achieving effective coverage and adherence.

Abstract Background Falls among older adults represent a major health hazard across the world. In 2022, the World Falls Guidelines was published, summarising research evidence and expert recommendations on how to prevent falls, but we need more knowledge on how the evidence can be successfully implemented into routine practice. In this study we used an implementation strategy co-created by healthcare providers, older adults who had fallen and researchers, to facilitate uptake of fall prevention recommendations. This current study aimed to evaluate the feasibility of this co-created implementation strategy in homecare services and provide information on the intervention and measurements for a full-scale cluster-randomized trial. Methods This study was a single-armed feasibility study with an embedded mixed-method approach completed in two city districts of Oslo, Norway, over a period of ten weeks. The co-created implementation strategy consists of a package for implementing national recommendations for preventing falls, empowering leaders to facilitate implementation, establish implementation teams, competence improvement and implementation support. City districts established implementation teams who were responsible for the implementation. Feasibility was assessed both qualitatively and quantitatively, using focus group interviews with implementation team members and individual interviews with leaders and staff members and the Feasibility of Intervention Measure (FIM). Qualitative data were analysed using thematic analysis and the Normalisation Process Theory. Results Qualitative data were collected from 19 participants: 12 implementation team members, 2 leaders and 5 staff members. 8 of the implementation team members responded to FIM. The analysis revealed four themes: 1) Fostering consensus through tailored implementation and discussions on fall prevention, 2) The importance of multi-level and interdisciplinary collaboration in fall prevention implementation, 3) Minimizing perceived time usage through utilization of existing areas for implementation activities, and 4) Reflective monitoring demonstrates the importance of facilitation and structure in the implementation strategy. For FIM, there were a high level of agreement related to how implementable, possible, doable, and easy to use the implementation strategy was. Conclusions Overall, we found the implementation strategy to be feasible to enhance uptake of fall prevention recommendations in the Norwegian homecare services. To succeed with the implementation, a dedicated implementation team should receive support through the implementation process, they should choose small implementation activities to enhance fall prevention competence and managers should possess implementation knowledge. Trial registration The trial is registered in the Open Science Registry: https://doi.org/10.17605/OSF.IO/2JFHV Registered: January 11, 2023.

Abstract Background Visna-maedi is a notifiable disease in Norway, and eliminating the disease is a national goal. The import of sheep into Norway is very limited, and strict regulations apply to the movement of small ruminants between flocks and within defined geographical regions. Several outbreaks have occurred in the last 50 years, and the most recent before 2019 occurred in Trøndelag county in Central Norway in 2002. A national surveillance programme for small ruminant lentivirus infection exists since 2003. Results In 2019, the national surveillance programme detected seropositive animals for small ruminant lentivirus in a sheep flock in Trøndelag. Based on the result of polymerase chain reaction analysis and histopathological findings, the Norwegian Food Safety Authority concluded the diagnosis of maedi. Further investigations detected maedi in eight additional sheep flocks in the same county. The flocks were placed under restrictions, and the authorities also imposed restrictions on 82 contact flocks. Sequencing of partial gag genes indicated that the virus in the current outbreak was related to the small ruminant lentivirus detected in the same area between 2002 and 2005. Conclusions The outbreak investigation shows the need for sensitive and specific diagnostic methods, and an improved and more targeted surveillance strategy. It also demonstrates the risk of disease spreading between flocks through animal movements, and highlights the importance of biosecurity and structured livestock trade. In addition to allowing livestock trade only from flocks documented free from maedi, it may be necessary to monitor sheep flocks over many years, when aiming to eliminate maedi from the Norwegian sheep population.

This paper discusses the significance of school curricula in reflecting societal priorities and needs, focusing on the incorporation of computational thinking (CT) in Nordic national curricula. Our point of departure is that the preparedness of future generations for a digitally driven society can be determined by analysing how CT is either explicitly or implicitly framed in school curricula. Accordingly, this study examined the school curricula of Denmark, Finland, and Norway in terms of their similarities and differences in how they framed CT, as these countries have different approaches to the inclusion of CT. A framework for analysis that was grounded in influential works on CT in education was developed, focusing on problem-solving, algorithmic and transversal practices. National-level curricula were examined using a content analysis. Despite the differences in the approaches used in these countries, our findings indicate similarities across all three curricula, with an emphasis on how CT was framed.

As computational thinking (CT) enters school curricula, and research on teaching of CT emerges, the time has come to spotlight CT in teacher education (TE). To this end, we conducted a literature review on CT in TE for STEM subjects with particular focus on research into pre-service teachers’ (PSTs) learning of pedagogical practices. We found 31 articles addressing CT in TE for STEM subjects between 2012 and 2023, applying qualitative, quantitative, and mixed methods, mainly with smaller sample sizes. Almost all describe teaching interventions with research on PSTs’ CT skills or attitudes. Only five articles include research questions explicitly addressing pedagogical practices for learning to teach CT. However, 13 articles explicitly describe such pedagogical practices and another seven implicitly do so. The review shows that the practices for teaching CT is an under-researched area, and the field lacks a common language and systematic research approaches. However, we do find that TE has clear ambitions for teaching PSTs about pedagogical practices as well as CT skills and attitudes.

The majority of bispecific costimulatory antibodies in cancer immunotherapy are capable of exerting tumor-specific T-cell activation by simultaneously engaging both tumor-associated targets and costimulatory receptors expressed by T cells. The amount of trimeric complex formed when the bispecific antibody is bound simultaneously to the T cell receptor and the tumor-associated target follows a bell-shaped curve with increasing bispecific antibody exposure/dose. The shape of the curve is determined by the binding affinities of the bispecific antibody to its two targets and target expression. Here, using the case example of FAP-4-1BBL, a fibroblast activation protein alpha (FAP)-directed 4-1BB (CD137) costimulator, the impact of FAP-binding affinity on trimeric complex formation and pharmacology was explored using mathematical modeling and simulation. We quantified (1) the minimum number of target receptors per cell required to achieve pharmacological effect, (2) the expected coverage of the patient population for 19 different solid tumor indications, and (3) the range of pharmacologically active exposures as a function of FAP-binding affinity. A 10-fold increase in FAP-binding affinity (from a dissociation constant [KD] of 0.7 nM–0.07 nM) was predicted to reduce the number of FAP receptors needed to achieve 90% of the maximum pharmacological effect from 13,400 to 4,000. Also, the number of patients with colon cancer that would achieve 90% of the maximum effect would increase from 6% to 39%. In this work, a workflow to select binding affinities for bispecific antibodies that integrates preclinical in vitro data, mathematical modeling and simulation, and knowledge on target expression in the patient population, is provided. The early implementation of this approach can increase the probability of success with cancer immunotherapy in clinical development.

BackgroundCambodia is targeting the elimination of malaria by 2025. The last remaining pockets of malaria in Cambodia are concentrated among populations exposed to forested areas, but the size of these populations is not well understood. To plan for the procurement and distribution of vector-control tools, chemoprophylaxis, and other commodities for malaria prevention and surveillance, robust estimates of the population at greatest risk are required. ObjectiveThis study aims to estimate the number of forest-exposed individuals residing in Cambodia’s highest-burden operational districts (ODs) in 2 provinces with active malaria transmission. MethodsIn April 2023, a multistage, in-person survey was conducted among residents in the 2 ODs in Cambodia with the highest malaria burden: Sen Monorom in Mondulkiri province and Phnom Srouch in Kampong Speu province. In each OD, 10 villages were randomly selected, and 35 households were randomly selected from each village. To estimate the number of individuals at high risk of malaria—defined as residing within 1 km of a forest or traveling at least once per week to the forest—respondents were asked about the distance from their household to the nearest forested area, and their travel patterns to forested areas. To account for mobility (ie, to avoid double-counting), respondents also provided information on overnight stays at other households in the selected villages in the past month. In the 4 selected villages in Sen Monorom OD where Project BITE forest packs (an intervention in the larger research program) had been distributed prior to the survey, respondents were also asked questions to determine if they had received such a pack, to develop smaller scale “multiplier method” estimates of at-risk individuals in each of those villages. ResultsIn Sen Monorom, 138 households and 872 individuals were enrolled in the survey, and in Phnom Srouch, 163 households and 844 individuals were enrolled. The estimated percentage of female householders was 49.7% (852/1716) across both ODs; the median age was 22 (IQR 12-37) years in Sen Monorom and 24.5 (IQR 16.0-40.5) years in Phnom Srouch (total age range 3-86). Based on mobility-adjusted survey estimates alone, 32% (280/706; 95% CI 19.9-47.2) of residents in Sen Monorom (an estimated 12,133-20,135 individuals) and 36% (68/198; 95% CI 24.5-45.5) of residents in Phnom Srouch (an estimated 1717-2203 individuals), met risk criteria for forest exposure. Between 125 and 186 individuals were estimated to be at risk in each of the 4 villages where the multiplier method could be applied. ConclusionsThis study provides estimates of the number of individuals potentially at high risk for malaria infection due to forest exposure in 2 ODs in Cambodia. These estimates can support planning for malaria control and elimination efforts. The straightforward methods of household surveys and multipliers should be feasible for many national malaria control programs.

IntroductionThe implementation of fall prevention interventions in homecare services is crucial for reducing falls among older adults and effective leadership could determine success. Norwegian homecare services provide home nursing, rehabilitation, and practical assistance, to residents living in private homes or assisted living facilities. This study aims to explore how managers in Norwegian homecare services experience implementation of fall prevention interventions and how they perceive their roles.MethodsWe conducted 14 semi-structured individual interviews with managers from different levels of homecare services in five city districts. The interviews were transcribed verbatim and reflexive thematic analysis was used to analyze the material.ResultsThe analysis resulted in three main themes: (1) understanding organizational mechanisms to facilitate new practices, (2) practicing positive leadership behavior to facilitate implementation, and (3) demonstrating persistence to sustain implementation. Our results showed the importance of clear leadership across all levels of the organization and the value of devoting time and utilizing existing systems. Managers described using recognition and positive attitudes to motivate employees in the implementation process. They emphasized listening to and involving employees, providing trust, and being flexible. However, the implementation process could be challenging, highlighting the need for managers to be persistent.ConclusionManagers at all levels play an important role in the implementation of fall prevention, but there is a need to define and align their specific roles in the process. Understanding how to use existing systems and influence through positive leadership behavior seem to be vital for success. Recognizing the demanding nature of implementation, managers emphasized the importance of systems for long term support. The study findings may influence how managers in clinical practice engage in the implementation process and inform future researchers about managers’ roles in implementation in homecare services.

Abstract Background The Great Mekong Subregion has attained a major decline in malaria cases and fatalities over the last years, but residual transmission hotspots remain, supposedly fueled by forest workers and migrant populations. This study aimed to: (i) characterize the fine-scale mobility of forest-goers and understand links between their daily movement patterns and malaria transmission, using parasites detection via real time polymerase chain reaction (RT PCR) and the individual exposure to Anopheles bites by quantification of anti-Anopheles saliva antibodies via enzyme-linked immunosorbent assay; (ii) assess the concordance of questionnaires and Global Positioning System (GPS) data loggers for measuring mobility. Methods Two 28 day follow-ups during dry and rainy seasons, including a GPS tracking, questionnaires and health examinations, were performed on male forest goers representing the population at highest risk of infection. Their time spent in different land use categories and demographic data were analyzed in order to understand the risk factors driving malaria in the study area. Results Malaria risk varied with village forest cover and at a resolution of only a few kilometers: participants from villages outside the forest had the highest malaria prevalence compared to participants from forest fringe’s villages. The time spent in a specific environment did not modulate the risk of malaria, in particular the time spent in forest was not associated with a higher probability to detect malaria among forest-goers. The levels of antibody response to Anopheles salivary peptide among participants were significantly higher during the rainy season, in accordance with Anopheles mosquito density variation, but was not affected by sociodemographic and mobility factors. The agreement between GPS and self-reported data was only 61.9% in reporting each kind of visited environment. Conclusions In a context of residual malaria transmission which was mainly depicted by P. vivax asymptomatic infections, the implementation of questionnaires, GPS data-loggers and quantification of anti-saliva Anopheles antibodies on the high-risk group were not powerful enough to detect malaria risk factors associated with different mobility behaviours or time spent in various environments. The joint implementation of GPS trackers and questionnaires allowed to highlight the limitations of both methodologies and the benefits of using them together. New detection and follow-up strategies are still called for.

Abstract Background The use of over-the-counter analgesics (OTCA) is common among adolescents and has been linked with increased symptoms of anxiety and depression. However, little is known about which specific symptoms are most strongly connected to OTCA usage. The current study assessed which anxiety and depression symptoms were most closely associated with OTCA usage in a large sample of adolescents and examined whether this differed across genders. Method The present study was based on data from 626,581 participants from the Ungdata survey in Norway. Associations between OTCA and anxiety and depression symptoms were examined using network analysis. Non-regularized partial-correlation networks were constructed to estimate the conditional dependent relations between the use of OTCA and symptoms while controlling for pain. Gender-specific networks were created for comparison. Results OTCA usage was associated with most symptoms, even after controlling for pain, with the strongest associations with “sleep problems”, “stiff or tense”, “everything is a struggle” and “suddenly scared”. There were some gender differences, showing that “sleep problems” and “hopeless” were more strongly related to OTCA usage in females, whereas “stiff or tense” was more strongly related to OTCA usage in males. Conclusion Overall, the somatic symptoms of anxiety and depression displayed the strongest associations with OTCA usage. When examining the gender-specific networks, both showed similar trends, although males exhibited slightly stronger associations between OTCA usage and somatic symptoms.

Abstract Background Physical or mental health comorbidities are common among people with substance use disorders undergoing opioid agonist therapy. As both a preventive and treatment strategy, exercise offers various health benefits for several conditions. Exercise interventions to people with substance use disorders receiving opioid agonist therapy are limited. This study aims to explore experiences with physical activity, perceived barriers, and facilitators among people receiving opioid agonist therapy. Method Fourteen qualitative interviews were conducted with individuals receiving opioid agonist therapy in outpatient clinics in Western Norway. Results Most were males in the age range 30 to 60 years. Participants had diverse and long-term substance use histories, and most received buprenorphine-based opioid agonist therapy. The identified themes were (1) Physical limitations: Participants experienced health-related problems like breathing difficulties, pain, and reduced physical function. (2) Social dynamics: Social support was essential for participating in physical activities and many argued for group exercises, but some were concerned about the possibility of meeting persons influenced by substances in a group setting, fearing temptations to use substances. (3) Shift in focus: As participants felt the weight of the health burden, their preference for activities shifted from sports aiming for “adrenaline” to a health promoting focus. (4) COVID-19’s impact on exercise: because of the pandemic, group activities were suspended, and participants described it as challenging to resume. (5) Implementation preferences in clinics: Not interfering with opioid medication routines was reported to be essential. Conclusion This study offers valuable insights for the development of customized exercise interventions aimed at enhancing the health and well-being of patients undergoing opioid agonist therapy. These findings underscore the significance of addressing social dynamics, overcoming physical limitations, and implementing a practical and effective exercise regimen.

Abstract People with substance use disorders often have unhealthy diets, high in sweets and processed foods but low in nutritious items like fruits and vegetables, increasing noncommunicable disease risks. This study investigates healthy eating perceptions and barriers among individuals with opioid use disorder undergoing opioid agonist therapy. Interviews with 14 participants at opioid agonist therapy clinics in Western Norway, using a semi-structured guide and systematic text condensation for analysis, reveal that most participants view their diet as inadequate and express a desire to improve for better health. Barriers to healthy eating included oral health problems, smoking habits, and limited social relations, while economic factors were less of a concern for the participants. Participants did find healthy eating easier when they were in social settings. This study underscores the importance of understanding and addressing these barriers and facilitators to foster healthier eating patterns in this population, potentially enhancing overall health and well-being.

Abstract Background Systematic reviews are viewed as the best study design to guide clinical decision-making as they are the least biased publications assuming they are well-conducted and include well-designed studies. Cochrane was initiated in 1993 with an aim of conducting high-quality systematic reviews. We aimed to examine the publication rates of non-Cochrane systematic reviews (henceforth referred to simply as “systematic reviews”) and Cochrane reviews produced throughout Cochrane’s existence and characterize changes throughout the period. Methods This observational study collected data on systematic reviews published between 1993 and 2022 in PubMed. Identified Cochrane reviews were linked to data from the Cochrane Database of Systematic Reviews via their Digital Object Identifier. Systematic reviews and Cochrane reviews were analyzed separately. Two authors screened a random sample of records to validate the overall sample, providing a precision of 98%. Results We identified 231,602 (94%) systematic reviews and 15,038 (6%) Cochrane reviews. Publication of systematic reviews has continuously increased with a median yearly increase rate of 26%, while publication of Cochrane reviews has decreased since 2015. From 1993 to 2002, Cochrane reviews constituted 35% of all systematic reviews in PubMed compared with 3.5% in 2013–2022. Systematic reviews consistently had fewer authors than Cochrane reviews, but the number of authors increased over time for both. Chinese first authors conducted 15% and 4% of systematic reviews published from 2013–2022 and 2003–2012, respectively. Most Cochrane reviews had first authors from the UK (36%). The native English-speaking countries the USA, the UK, Canada, and Australia produced a large share of systematic reviews (42%) and Cochrane reviews (62%). The largest publishers of systematic reviews in the last 10 years were gold open access journals. Conclusions Publication of systematic reviews is increasing rapidly, while fewer Cochrane reviews have been published through the last decade. Native English-speaking countries produced a large proportion of both types of systematic reviews. Gold open access journals and Chinese first authors dominated the publication of systematic reviews for the past 10 years. More research is warranted examining why fewer Cochrane reviews are being published. Additionally, examining these systematic reviews for research waste metrics may provide a clearer picture of their utility.

Somatic cell count (SCC) is a widely used indicator of milk quality in the dairy industry. It is a relatively good indicator of udder health in dairy cows, but strongly confounded by non-infection factors, including season, in dairy goats. This study's objectives were to estimate the variation in SCC explained by season and stage of lactation. We also investigated associations between SCC and other milk quality parameters routinely measured, including total bacterial count, fat, protein, and lactose content, in different seasons and stages of lactation. In this observational study, we included results from the routine analyses of bulk milk samples (n = 5,180) collected every third day in 88 Norwegian goat herds through one year. Herd information was collected via a questionnaire and from the dairy herd recording system. The herds had a notable increase in bulk SCC associated with the pasture season. The median bulk SCC was 470,000 cells/mL in deliveries from the indoor spring period and 1,100,000 cells/mL in the pasture season. During the indoor fall season, when most goat herds are in late lactation, the median SCC was 940,000 cells/mL. The combined effect of the season and herd stage of lactation explained 53.5% of the variation in bulk milk SCC. Fat and protein contents varied significantly with season and stage of lactation, and the association with SCC was non-significant for fat content and explained less than 3% of the variation in protein content. Lactose content was associated with SCC, stage of lactation, and season. Total bacterial count was associated with SCC and the indoor seasons. Determination of normal seasonal variation of goat bulk milk SCC is necessary to establish thresholds for defining milk as abnormal and unacceptable for further processing and improving the usefulness of SCC as a tool for milk quality improvement in dairy goats. The results suggest that SCC thresholds for taking action to improve the milk quality should be adjusted for season and stage of lactation.

Abstract Background Stress impacts healthy behaviours and may influence life and health-related quality of life (HRQOL). A stressful event occurred when the COVID-19 pandemic hit in March 2020. The present study aims to explore possible gender differences in stress, psychosocial factors (self-efficacy, self-esteem, loneliness), pain, HL, and HRQOL in parents of adolescents one year into the COVID-19 pandemic, and to explore possible associations between gender, demographic and psychosocial factors, pain, HL, and HRQOL. Methods Parents of adolescents aged 16–17 took part in the study from January to February 2021, when the COVID-19 pandemic was ongoing. Data on socio-demographics, stress, self-efficacy, self-esteem, pain, HL, loneliness, and HRQOL were collected. HRQOL was assessed using RAND-36. Results Among the 320 parents from the general population, the mean age was 47.6 (standard deviation (SD) = 4.6) years, 81% were mothers, 79% were married or cohabiting, 81% had a university degree, and the majority worked full time (78%) or part time (13%). The average pain score was low, 0.48 (95% CI [0.43–0.54]). However, 50% of the parents reported persistent pain and more mothers reported persistent pain compared to fathers (53% vs. 37%). The parents’ mean (SD) score for RAND-36 was 52.1 (95% CI [51.2–53.0]) for the physical component summary (PCS) score and 51.0 (95% CI [50.0–52.1]) for the mental component summary (MCS) score. Mothers reported significantly lower scores for all the eight RAND-36 domains and the PCS and MCS scores. Adjusting for gender, age, living condition, education, pain, HL, self-efficacy and loneliness, we revealed no associations between stress and RAND-36-PCS. University education of four years or more was positively associated (B = 3.29, 95% CI: [0.78–5.80]) with RAND-36-PCS, while persistent pain was negatively associated (B = -7.13, CI: [-9.20– -5.06]). We identified a strong negative association between RAND-36-MCS and stress (B = -43.11, CI: [-48.83– -37.38]) and a positive association with older age (B = 0.21, CI: [ 0.04, 0.39)]. Conclusion One year into the COVID-19 pandemic, we identified a strong negative association between stress and mental HRQOL, while pain was strongly negatively associated with physical HRQOL.

Summary: Background & Aims: Adequate nutritional care to malnourished patients is described as a human right, and recommendations from nutritional care guidelines are legally binding in Norway. The primary objective of this study was to investigate nutritional care in malnourished hospitalized patients. We also wanted to describe the association between malnutrition and length of stay (LOS), readmission, comorbidity and mortality. Methods: In a cross-sectional, multi-center and quality assurance study, inpatients from four university hospitals across all regional health authorities in Norway were included. The hospital's nutritional care during admission was evaluated according to current malnutrition guidelines. Malnutrition risk screening, assessment for diagnosis and grading severity of malnutrition were performed with Nutritional risk screening 2002 (NRS-2002) and the Global Leadership Initiative on malnutrition (GLIM) criteria. Medical records were reviewed to collect data on nutritional support during admission, malnutrition coding, LOS, readmission, comorbidity and 30-days survival after hospital admission. Results: In our mixed inpatient population (n 442, mean age 61 years, 53 % women), 42 % were not adequately screened for risk of malnutrition at hospital admission. Among the 29 % of malnourished patients, only 36 % had documented nutritional support in the medical records, and a malnutrition diagnosis was registered for only 30 %. Malnutrition was associated with LOS, increased comorbidity and reduced 30-day survival. Conclusion: In this study across all Norwegian regional health authorities, we found a high malnutrition rate and the nutritional care in relation to malnutrition diverged from national and international established guidelines and the framework of national laws and legislation. The findings raise concerns regarding patient safety and potential for improved nutritional care as a human right. Although malnutrition was associated with longer length of hospital stay, comorbidity and reduced 30-day survival, this study does not establish causal relationships.

Abstract Malaria remains a global health challenge, disproportionately affecting vulnerable communities. Despite substantial progress, the emergence of anti-malarial drug resistance poses a constant threat. The Greater Mekong Subregion (GMS), which includes Cambodia, China’s Yunnan province, Lao People's Democratic Republic, Myanmar, Thailand, and Viet Nam has been the epicentre for the emergence of resistance to successive generations of anti-malarial therapies. From the perspective of the World Health Organization (WHO), this article considers the collaborative efforts in the GMS, to contain Plasmodium falciparum artemisinin partial resistance and multi-drug resistance and to advance malaria elimination. The emergence of artemisinin partial resistance in the GMS necessitated urgent action and regional collaboration resulting in the Strategy for Malaria Elimination in the Greater Mekong Subregion (2015–2030), advocating for accelerated malaria elimination interventions tailored to country needs, co-ordinated and supported by the WHO Mekong malaria elimination programme. The strategy has delivered substantial reductions in malaria across all GMS countries, with a 77% reduction in malaria cases and a 97% reduction in malaria deaths across the GMS between 2012 and 2022. Notably, China was certified malaria-free by WHO in 2021. Countries' ownership and accountability have been pivotal, with each GMS country outlining its priorities in strategic and annual work plans. The development of strong networks for anti-malarial drug resistance surveillance and epidemiological surveillance was essential. Harmonization of policies and guidelines enhanced collaboration, ensuring that activities were driven by evidence. Challenges persist, particularly in Myanmar, where security concerns have limited recent progress, though an intensification and acceleration plan aims to regain momentum. Barriers to implementation can slow progress and continuing innovation is needed. Accessing mobile and migrant populations is key to addressing remaining transmission foci, requiring effective cross-border collaboration. In conclusion, the GMS has made significant progress towards malaria elimination, particularly in the east where several countries are close to P. falciparum elimination. New and persisting challenges require sustained efforts and continued close collaboration. The GMS countries have repeatedly risen to every obstacle presented, and now is the time to re-double efforts and achieve the 2030 goal of malaria elimination for the region.

Abstract Visual hallucinations in psychosis are under-researched despite associations with increased illness severity, functional impairments, and suicidality in the few existing studies. Further, there are no long-term longitudinal studies, making it impossible to conclude if these associations are state or trait phenomena. In the current prospective longitudinal study, 184 individuals with first-episode psychosis were assessed with semi-structured clinical interviews and self-report questionnaires at baseline and 10-year follow-up. Participants were grouped based on lifetime experience of visual hallucinations: before or at baseline (VH+/+), first during follow-up (VH−/+), or never (VH−/−). Associations with functioning, suicide attempts, childhood trauma and other markers of illness severity were tested using multinomial logistic regression analysis. At baseline, the VH+/+ group (37.5%), but not VH−/+ (12.5%), had poorer functioning, higher symptom severity, a lower age at onset, and included more individuals with a history of multiple suicide attempts than the VH−/− group (50%). At follow-up, the VH−/+ group, but not VH+/+, had poorer functioning and higher symptom severity than the VH−/− group. However, the number of participants who committed multiple suicide attempts during the follow-up period was again significantly higher in the VH+/+ group. There was no association with childhood trauma. Hence, visual hallucinations are associated with impaired functioning and higher symptom severity, but only in the short-term. However, visual hallucinations that arise early in the course of illness are a risk indicator for repeated suicide attempts throughout the illness course. These findings highlight the relevance of assessing visual hallucinations and monitoring their development over time.

Objective Some brachial cuffs for oscillometric blood pressure (BP) measurement are claimed to cover a wide range of upper-arm circumferences; however, their validation is rarely conducted. Our aim was to compare oscillometric BP measurements obtained with a universal cuff with those obtained with an appropriately sized cuff.Methods We utilised the Microlife B6 Connect monitor, conducting oscillometric BP measurements in a random sequence with both a universal cuff (recommended for arm circumferences from 22 to 42 cm) and an appropriately sized cuff (medium for circumference 22–32 cm and large for 32–42 cm). We included 91 individuals with an arm circumference of 22–32 cm and 64 individuals with an arm circumference of 32–42 cm.Results For arm circumferences > 32 cm, systolic and diastolic BP measured with the universal cuff was higher than that measured with the large cuff (systolic 6.4 mmHg, 95% confidence interval [CI]). 3.9–8.8, diastolic 2.4 mmHg, 95%CI, 1.2–3.7, p

Abstract Aim The aim of the study was to understand the experiences of nurses who were newly appointed to a position of leadership including facilitators and barriers to success and what they considered important for the development of their role. Methods We used a qualitative descriptive research design. The study was conducted in Norway with 10 nurses who had been appointed to a leadership position within the last 2 years. Participants were interviewed with individual qualitative interviews which were transcribed and subsequently analysed using thematic analysis. Results The following four main themes were identified from the data: I feel lonely in the leadership position, I am not confident as a leader, I am unsure of the requirements and expectations of me, and I need support and supervision. Conclusion The results underscore the challenges reported by new leaders in nursing and their advocacy for mentorship as a facilitator for success. The qualifications of mentors were emphasised with a need for a comprehensive leadership skill set to address the multifaceted aspects of leadership development.

Abstract Background Cambodia aims to eliminate all forms of malaria by 2025. In 2020, 90% of all malaria cases were Plasmodium vivax. Thus, preventing P. vivax and relapse malaria is a top priority for elimination. 14-day primaquine, a World Health Organization-recommended radical cure treatment regimen, specifically targets dormant hypnozoites in the liver to prevent relapse. Cambodia introduced P. vivax radical cure with primaquine after glucose-6-phosphate dehydrogenase (G6PD) qualitative testing in 2019. This paper presents Cambodia’s radical cure Phase I implementation results and assesses the safety, effectiveness, and feasibility of the programme prior to nationwide scale up. Methods Phase I implementation was carried out in 88 select health facilities (HFs) across four provinces. Males over 20kgs with confirmed P. vivax or mixed (P. vivax and Plasmodium falciparum) infections were enrolled. A descriptive analysis evaluated the following: successful referral to health facilities, G6PD testing results, and self-reported 14-day treatment adherence. P. vivax incidence was compared before and after radical cure rollout and a controlled interrupted time series analysis compared the estimated relapse rate between implementation and non-implementation provinces before and after radical cure. Results In the 4 provinces from November 2019 to December 2020, 3,239 P. vivax/mixed infections were reported, 1,282 patients underwent G6PD deficiency testing, and 959 patients received radical cure, achieving 29.6% radical cure coverage among all P. vivax/mixed cases and 98.8% coverage among G6PD normal patients. Among those who initiated radical cure, 747 patients (78%) completed treatment. Six patients reported side effects. In implementation provinces, an average 31.8 relapse cases per month were estimated signaling a 90% (286 cases) reduction in relapse compared to what would be expected if radical cure was not implemented. Conclusions Plasmodium vivax radical cure is a crucial tool for malaria elimination in Cambodia. The high coverage of radical cure initiation and adherence among G6PD normal patients demonstrated the high feasibility of providing radical cure at point of care in Cambodia. Incomplete referral from community to HFs and limited capacity of HF staff to conduct G6PD testing in high burden areas led to lower coverage of G6PD testing. Phase I implementation informed approaches to improve referral completion and patient adherence during the nationwide expansion of radical cure in 2021.

Abstract Obesity is associated with an increased risk of developing multiple myeloma (MM). The molecular mechanisms causing this association is complex and incompletely understood. Whether obesity affects bone marrow immune cell composition in multiple myeloma is not characterized. Here, we examined the effect of diet-induced obesity on bone marrow immune cell composition and tumor growth in a Vk*MYC (Vk12653) transplant model of multiple myeloma. We find that diet-induced obesity promoted tumor growth in the bone marrow and spleen and reduced the relative number of T and B cells in the bone marrow. Our results suggest that obesity may reduce MM immune surveillance and thus may contribute to increased risk of developing MM.

Abstract Background Despite substantial research evidence indicating the effectiveness of a range of interventions to prevent falls, uptake into routine clinical practice has been limited by several implementation challenges. The complexity of fall prevention in municipality health care underlines the importance of flexible implementation strategies tailored both to general determinants of fall prevention and to local contexts. This cluster-randomised trial (RCT) investigates the effectiveness of a tailored intervention to implement national recommendations on fall prevention among older home-dwelling adults compared to usual practice on adherence to the recommendations in health professionals. Methods Twenty-five municipalities from four regions in Norway will be randomised to intervention or control arms. Each municipality cluster will recruit up to 30 health professionals to participate in the study as responders. The tailored implementation intervention comprises four components: (1) identifying local structures for implementation, (2) establishing a resource team from different professions and levels, (3) promoting knowledge on implementation and fall prevention and (4) supporting the implementation process. Each of these components includes several implementation activities. The Consolidated Framework for Implementation Research (CFIR) will be used to categorise determinants of the implementation process and the Expert Recommendations for Implementing Change (ERIC) will guide the matching of barriers to implementation strategies. The primary outcome measure for the study will be health professionals’ adherence to the national recommendations on fall prevention measured by a questionnaire. Secondary outcomes include injurious falls, the feasibility of the intervention, the experiences of the implementation process and intervention costs. Measurements will be carried out at baseline in August 2023, post-intervention in May 2024 and at a follow-up in November 2024. Discussion This study will provide evidence on the effectiveness, intervention costs and underlying processes of change of tailored implementation of evidence-based fall prevention recommendations. Trial registration The trial is registered in the Open Science Registry: https://doi.org/10.17605/OSF.IO/JQ9T5 . Registered: March 03, 2023.

Abstract Background Research focusing on the association between serum vitamin D and oral health outcomes in children, such as dental caries and molar incisor hypomineralisation (MIH), shows inconsistent results. Previous studies have predominantly investigated dental caries and MIH as dichotomized outcomes, which limits the information on their distribution. In addition, the methods used for analysing serum vitamin D have varied. The present study aimed to investigate potential associations between serum vitamin D status measured by Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS) and the prevalence, as well as the number of teeth, affected by dental caries or MIH among 7–9-year-old Norwegian children. Methods The study had a cross-sectional design and included 101 children aged 7–9 years. Serum 25-hydroxyvitamin D (25(OH)D) was measured and included as continuous (per 25 nmol/l) and categorised (insufficient (

The Norwegian government approves farm-based education for pupils who do not benefit sufficiently from ordinary school. The aim of this article is to contribute knowledge on secondary school pupilsʼ experiences of such programs, and how they affect inner motivation for school. The article is based on qualitative interviews with thirteen pupils in years nine and ten (ages 14-16) from farms located in different regions of Norway. The pupils experienced the farmersʼ care and involvement, became part of a safe and inclusive community, were given the opportunity to try varied practical activities, experienced personal development, and gained new motivation for school. Using basic psychological needs theory and recovery theory, it is found that the pupils experienced relatedness to other pupils and to the farmers, improved their social and practical competence, and experienced autonomy (self-determination) through voluntary participation. The farmers and the community can be described as autonomy-supportive and “restitution-nourishing” and as contributing to personal development and the development of inner motivation. This strengthened the pupilsʼ self-confidence, hope for the future, and their attention in and efforts at school. The findings from the study indicate that motivation developed in one learning context (the farm) can influence the motivation for another context (ordinary school).

The aim of this study was to investigate eighth-grade students’ assessment literacy and writing skills in English as a foreign language using an AI-based automated essay assessment tool (EAT). Data were gathered from a design-based research initiative where the EAT was designed, developed, and tested in naturalistic school settings. Fifty-six eighth-grade students wrote individual essays, for which they received automatic feedback. The feedback was discussed with their teachers and peers. Both the writing process and teacher and peer interactions were video recorded. The video data were analyzed using an interaction analysis. The improvements made on the essay based on the feedback logs registered by the EAT for each student’s writing trajectory and the different versions of the essay were examined using frequency analyses. The findings demonstrate that automated essay assessment might be useful for fostering students’ writing skills if teachers help students get started, identify errors, and share interpretations.

In this article, we study how language majority and minority youth (Finnish-, Swedish- and Sami-speaking youth) in Finland and Sweden perceive the possibility to use languages in their countries. Our theoretical underpinnings are inspired by language policy and language ecology with a special focus on possible impacts of national language policy on language ideologies and language praxis circulating in increasingly multilingual societies. The results show that several statistically significant differences can be revealed between the youth from different countries and with different first languages. The differences indicate that national policy seems to have an effect on language ideologies among the participants. Nevertheless, the youth shares a common belief of the importance of multilingualism even if they recognize the practical challenges that people who cannot use the majority language of the country can face. Language is perceived not only as a medium for communication but also as an important part of the individual’s identity and culture. The result of this study shows that the youth perceives the use of different languages in their country of residence as self-evident.

In this article, we focus on the language practices of teaching Swedish as second national language in Finnish-medium primary schools. We examine teacher perceptions of the linguistic repertoires of the student group as well as of language use and language choices in the classroom. The analysis is based on interviews with teachers of different Swedish syllabi. The results show that some Swedish teachers see their students and groups as monolingual, while others both see and strive to acknowledge the students’ multilingualism. In general, the Swedish teachers consider themselves aware of the students' linguistic backgrounds. The study further shows that there is variation in the use and dominance of individual languages in Swedish teaching, with focus on Swedish and Finnish, and that there are differences in how teachers perceive language use and language choice between the different actors in the classroom. These differences are related to the characteristics of the three syllabi and divergences in the local linguistic contexts. Although all teachers who participated in this study teach the subject of Swedish as second national language, their descriptions of the language practices varied in terms of language choices and multilingualism in the classroom. The pattern that emerges is that communication in the classroom according to the teachers is more Swedish-dominated in the native-level Swedish syllabus whereasthe classroom in the B1-Swedish syllabus is more Finnish-dominated. The linguistic practices in A-Swedish classrooms move between these two alternatives. The study gives insight to the de facto language policy of the classroom, which is of central importance for the possibility of enhancing a language pedagogy in accordance with today’s approach to language teaching and multilingualism.

Abstract Background The uptake of fall prevention evidence has been slow and limited in home care services. Involving stakeholders in the implementation process is suggested as a method to successfully tailor implementation strategies. The aim of this study was to develop an implementation strategy for fall prevention, targeting healthcare providers working in home care services. Methods This study used an explorative qualitative approach in a five-step co-creation process to involve researchers, service users, and healthcare providers. The first two steps consisted of workshops. This was followed by focus group interviews and individual interviews with key informants as steps three and four. Data from the first four steps were analyzed using reflexive thematic analysis. The fifth and final step was a workshop finalizing a strategy for implementing fall prevention evidence in home health services. Results Overall, our findings, resulted in an implementation strategy for fall prevention with four components: (1) Empower leaders to facilitate implementation, operationalized through what managers pay attention to regularly, resource priorities, and time spent on fall prevention, (2) Establish implementation teams, consisting of multidisciplinary healthcare providers from different levels of the organization, with formalized responsibility for implementation, (3) Tailor dual competence improvement, reflecting the need for knowledge and skills for fall prevention and implementation among healthcare providers and users, and (4) Provide implementation support, representing guidance through the implementation process. Conclusions This study advances our understanding of implementation in home care services. Implementation of fall prevention requires an implementation strategy involving a blend of essential components targeting leaders, competent healthcare providers and users, and establishing structures enhancing the implementation process.

I denne artikkelen er det barnevernsstudenters bruk av refleksjonstekster som er utgangspunktet. Artikkelen utforsker hvordan studentene tar i bruk refleksjonstekster gjennom et emne, for så å drøfte hvilke bidrag slike tekster kan ha i profesjonsstudier der studentsentrerte læringsformer er sentrale. I tekstene reflekterer studentene over hvordan det er å være student i emnet, og hva de erfarer at hemmer eller fremmer deres læring og deres kvalifisering til barnevernspedagog. Analysen viser at studentene tar i bruk refleksjonstekstene på ulike måter, og at graden av refleksjon varierer. Tekstene gir innsikt i studentenes holdning til læring og utvikling og kan derfor være gode bidrag i utformingen av studentsentrerte læringsmiljøer.

Introduction: Approximately 20% of Norwegian adolescents are frequently using Over-the-Counter Analgesics (OTCAs). The WHO emphasizes the need for research to identify the key determinants of health problems in adolescence. Thus, our aim was to describe and explore pain, stress, and Health-Related Quality of Life (HRQOL) in Norwegian adolescents and investigate possible associations upon high/low usage of OTCAs. Methods: This cross-sectional study included 315 adolescents (92 boys, 223 girls) with an average age of 14.1 years (13–15 years). All participants reported using OTCAs. Weekly usage was categorized as high and less than weekly as low. Using a validated questionnaire, we explored the following variables: pain, as measured using the Brief Pain Inventory, stress (Perceived Stress Questionnaire), and HRQOL (KIDSSCREEN-27). Binary logistic regression models were conducted using IBM SPSS Statistics (version 27). Results: Our descriptive findings reveal that high users of OTCAs reported higher pain intensity of 3.4 (SD = 1.9) and perceived stress of 0.38 (SD = 0.18) compared to low users, who reported 2.5 (SD = 1.9) and 0.32 (SD = 0.16), respectively. High OTCA users reported lower average scores than low users across all HRQOL subscales. Binary logistic regression revealed 30% higher odds for higher levels of pain intensity and 14 times higher odds of perceived stress associated with being a high user of OTCAs compared to a low user. Conclusions: Our study shows significantly higher odds for experiencing pain and stress among adolescents using OTCAs daily-to-weekly, compared to those seldom using such medicines. Health professionals should be aware of young people who have a high consumption of OTCAs and investigate whether the use is related to pain or stress. This might be important in designing a personalized and appropriate intervention. Parents and caregivers have an important responsibility in supporting adolescents’ appropriate pain management. Longitudinal studies are needed to better explore predictive factors of OTCA use in adolescents, particularly in relation to psychological variables such as stress and quality of life.

Previous studies suggest that older adults from minority linguistic groups are at a higher risk of experiencing social exclusion, with service exclusion being a highly evident form. This article explores how Swedish- speaking older adults in Finland experience the availability and adequacy of services in their first language and how their experiences are linked to social exclusion. Anchored in the intersection between two dimensions of social exclusion, service exclusion and identity exclusion, this study presents findings from 14 semi-structured interviews with uni- and bilingual Swedish-speaking older adults. The results indicate that inequitable access to services and facing language discordant services can shape experiences of exclusion. The inability to receive everyday services in Swedish further fosters feelings of inferiority and identity discrimination. This study findings contribute to the social gerontological literature on social exclusion and demonstrate how identity intersections with service exclusion.

Introduction Improving the health of Indigenous adolescents is central to addressing the health inequities faced by Indigenous peoples. To achieve this, it is critical to understand what is needed from the perspectives of Indigenous adolescents themselves. There have been many qualitative studies that capture the perspectives of Indigenous young people, but synthesis of these has been limited to date.Methods and analysis This scoping review seeks to understand the specific health needs and priorities of Indigenous adolescents aged 10–24 years captured via qualitative studies conducted across Australia, Aotearoa New Zealand, Canada, the USA, Greenland and Sami populations (Norway and Sweden). A team of Indigenous and non-Indigenous researchers from these nations will systematically search PubMed (including the MEDLINE, PubMed Central and Bookshelf databases), CINAHL, Embase, Scopus, the Informit Indigenous and Health Collections, Google Scholar, Arctic Health, the Circumpolar Health Bibliographic Database, Native Health Database, iPortal and NZresearch.org, as well as specific websites and clearinghouses within each nation for qualitative studies. We will limit our search to articles published in any language during the preceding 5 years given that needs may have changed significantly over time. Two independent reviewers will identify relevant articles using a two-step process, with disagreements resolved by a third reviewer and the wider research group. Data will then be extracted from included articles using a standardised form, with descriptive synthesis focussing on key needs and priorities. This scoping review will be conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines.Ethics and dissemination Ethics approval was not required for this review. Findings will be disseminated via a peer-reviewed journal article and will inform a broader international collaboration for Indigenous adolescent health to develop evidence-based actions and solutions.

Abstract The dose/exposure‐efficacy analyses are often conducted separately for oncology end points like best overall response, progression‐free survival (PFS) and overall survival (OS). Multistate models offer to bridge these dose‐end point relationships by describing transitions and transition times from enrollment to response, progression, and death, and evaluating transition‐specific dose effects. This study aims to apply the multistate pharmacometric modeling and simulation framework in a dose optimization setting of bintrafusp alfa, a fusion protein targeting TGF‐β and PD‐L1. A multistate model with six states (stable disease [SD], response, progression, unknown, dropout, and death) was developed to describe the totality of endpoints data (time to response, PFS, and OS) of 80 patients with non‐small cell lung cancer receiving 500 or 1200 mg of bintrafusp alfa. Besides dose, evaluated predictor of transitions include time, demographics, premedication, disease factors, individual clearance derived from a pharmacokinetic model, and tumor dynamic metrics observed or derived from tumor size model. We found that probabilities of progression and death upon progression decreased over time since enrollment. Patients with metastasis at baseline had a higher probability to progress than patients without metastasis had. Despite dose failed to be statistically significant for any individual transition, the combined effect quantified through a model with dose‐specific transition estimates was still informative. Simulations predicted a 69.2% probability of at least 1 month longer, and, 55.6% probability of at least 2‐months longer median OS from the 1200 mg compared to the 500 mg dose, supporting the selection of 1200 mg for future studies.

Abstract FAP‐4‐1BBL is a bispecific antibody exerting 4‐1BB‐associated T‐cell activation only while simultaneously bound to the fibroblast activation protein (FAP) receptor, expressed on the surface of cancer‐associated fibroblasts. The trimeric complex formed when FAP‐4‐1BBL is simultaneously bound to FAP and 4‐1BB represents a promising mechanism to achieve tumor‐specific 4‐1BB stimulation. We integrated in vitro data with mathematical modeling to characterize the pharmacology of FAP‐4‐1BBL as a function of trimeric complex formation when combined with the T‐cell engager cibisatamab. This relationship was used to prospectively predict a range of clinical doses where trimeric complex formation is expected to be at its maximum. Depending on the dosing schedule and FAP‐4‐1BBL plasma: tumor distribution, doses between 2 and 145 mg could lead to maximum trimeric complex formation in the clinic. Due to the expected variability in both pharmacokinetic and FAP expression in the patient population, we predict that detecting a clear dose–response relationship would remain difficult without a large number of patients per dose level, highlighting that mathematical modeling techniques based on in vitro data could aid dose selection.

AbstractThe ‘Oslo Chronic Fatigue Consortium’ consists of researchers and clinicians who question the current narrative that chronic fatigue syndromes, including post-covid conditions, are incurable diseases. Instead, we propose an alternative view, based on research, which offers more hope to patients. Whilst we regard the symptoms of these conditions as real, we propose that they are more likely to reflect the brain's response to a range of biological, psychological, and social factors, rather than a specific disease process. Possible causes include persistent activation of the neurobiological stress response, accompanied by associated changes in immunological, hormonal, cognitive and behavioural domains. We further propose that the symptoms are more likely to persist if they are perceived as threatening, and all activities that are perceived to worsen them are avoided. We also question the idea that the best way to cope with the illness is by prolonged rest, social isolation, and sensory deprivation.Instead, we propose that recovery is often possible if patients are helped to adopt a less threatening understanding of their symptoms and are supported in a gradual return to normal activities. Finally, we call for a much more open and constructive dialogue about these conditions. This dialogue should include a wider range of views, including those of patients who have recovered from them.

Abstract Background The SafeBoosC project aims to test the clinical value of non-invasive cerebral oximetry by near-infrared spectroscopy in newborn infants. The purpose is to establish whether cerebral oximetry can be used to save newborn infants’ lives and brains or not. Newborns contribute heavily to total childhood mortality and neonatal brain damage is the cause of a large part of handicaps such as cerebral palsy. The objective of the SafeBoosC-IIIv trial is to evaluate the benefits and harms of cerebral oximetry added to usual care versus usual care in mechanically ventilated newborns. Methods/design SafeBoosC-IIIv is an investigator-initiated, multinational, randomised, pragmatic phase-III clinical trial. The inclusion criteria will be newborns with a gestational age more than 28 + 0 weeks, postnatal age less than 28 days, predicted to require mechanical ventilation for at least 24 h, and prior informed consent from the parents or deferred consent or absence of opt-out. The exclusion criteria will be no available cerebral oximeter, suspicion of or confirmed brain injury or disorder, or congenital heart disease likely to require surgery. A total of 3000 participants will be randomised in 60 neonatal intensive care units from 16 countries, in a 1:1 allocation ratio to cerebral oximetry versus usual care. Participants in the cerebral oximetry group will undergo cerebral oximetry monitoring during mechanical ventilation in the neonatal intensive care unit for as long as deemed useful by the treating physician or until 28 days of life. The participants in the cerebral oximetry group will be treated according to the SafeBoosC treatment guideline. Participants in the usual care group will not receive cerebral oximetry and will receive usual care. We use two co-primary outcomes: (1) a composite of death from any cause or moderate to severe neurodevelopmental disability at 2 years of corrected age and (2) the non-verbal cognitive score of the Parent Report of Children’s Abilities-Revised (PARCA-R) at 2 years of corrected age. Discussion There is need for a randomised clinical trial to evaluate cerebral oximetry added to usual care versus usual care in mechanically ventilated newborns. Trial registration The protocol is registered at www.clinicaltrials.gov (NCT05907317; registered 18 June 2023).

Erectile dysfunction is a known late complication following surgery for rectal cancer. We aimed to determine the prevalence of erectile dysfunction after rectal cancer surgery and characterize it. This was a prospective observational cohort study. Data from men after surgery for rectal cancer were collected between October 2019 and April 2023. The primary outcome was the prevalence of erectile dysfunction following surgery based on the International Index of Erectile Function questionnaires, IIEF-5 and 15. Secondary outcomes were prevalence in subgroups and self-perceived erectile function. In total, 101 patients agreed to participate, while 67 patients (67%) responded after a median six-month follow-up after surgery. Based on IIEF-15, 84% of the patients had erectile dysfunction. For subgroups, 74% of patients who underwent robot-assisted surgery had erectile dysfunction, whereas all patients who underwent either laparoscopic or open surgery had erectile dysfunction (p = 0.031). Furthermore, half of the patients rated their self-perceived ability to obtain and keep an erection as very low. In conclusion, in our cohort, erectile dysfunction was common after rectal cancer surgery, and half of the patients were unconfident that they could obtain and keep an erection. Information regarding this finding should be given so that patients feel comfortable discussing therapeutic solutions if needed.

Abstract Background In the SafeBoosC-III trial, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth did not reduce the incidence of death or severe brain injury in extremely preterm infants at 36 weeks’ postmenstrual age, as compared with usual care. Despite an association between severe brain injury diagnosed in the neonatal period and later neurodevelopmental disability, this relationship is not always strong. The objective of the SafeBoosC-III follow-up study is to assess mortality, neurodevelopmental disability, or any harm in trial participants at 2 years of corrected age. One important challenge is the lack of funding for local costs for a trial-specific assessment. Methods Of the 1601 infants randomised in the SafeBoosC-III trial, 1276 infants were alive at 36 weeks’ postmenstrual age and will potentially be available for the 2-year follow-up. Inclusion criteria will be enrollment in a neonatal intensive care unit taking part in the follow-up study and parental consent if required by local regulations. We aim to collect data from routine follow-up programmes between the ages of 18 and 30 months of corrected age. If no routine follow-up has been conducted, we will collect informal assessments from other health care records from the age of at least 12 months. A local co-investigator blinded to group allocation will classify outcomes based on these records. We will supplement this with parental questionnaires including the Parent Report of Children’s Abilities—Revised. There will be two co-primary outcomes: the composite of death or moderate or severe neurodevelopmental disability and mean Bayley-III/IV cognitive score. We will use a 3-tier model for prioritisation, based on the quality of data. This approach has been chosen to minimise loss to follow-up assuming that little data is better than no data at all. Discussion Follow-up at the age of 2 years is important for intervention trials in the newborn period as only time can show real benefits and harms later in childhood. To decrease the risk of generalisation and data-driven biased conclusions, we present a detailed description of the methodology for the SafeBoosC-III follow-up study. As funding is limited, a pragmatic approach is necessary. Trial registration ClinicalTrials.gov NCT05134116 . Registered on 24 November 2021.

Abstract Background Insufficient sleep is commonly reported in adolescence and is negatively associated with a wide range of health outcomes. A way to grasp the complicated challenge of how sleep impact different aspects of the adolescents´ everyday life is by examining the relationship between sleep duration in schooldays and weekends on different health-related quality of life (HRQOL) subscales. Furthermore, to expand the understanding of possible underlying mechanisms between sleep and HRQOL, testing for self-efficacy as a possible mediator is of importance. Methods A cross-sectional study was performed among 696 adolescents aged 13–15 years from a school-based setting. All participants completed an electronic survey in their respective classrooms. The survey included demographic data, the School Sleep Habits Survey, the KIDSCREEN-27 questionnaire measuring HRQOL, and the General Perceived Self-Efficacy Scale. Statistical analyses were conducted using SPSS Statistics software including PROCESS macro by Andrew Hayes. Results Our findings revealed overall similar sleep patterns in boys and girls including longer sleep duration in the study sample during weekends (10:09 h) than in schooldays (08:36 h). Regression analyses revealed that sleep duration in schooldays was positively and statistically associated with HRQOL subscales psychological well-being (95% CI [0.44 to 1.33]), autonomy and parents (95% CI [0.12 to 1.06]), school environment (95% CI [0.47 to 1.40]), and self-efficacy (95% CI [0.01 to 0.47]). Sleep duration in weekends revealed no associations with the HRQOL subscales, except for the HRQOL subscale psychological well-being (95% CI [0.09 to 0.85]). Mediation analyses revealed that sleep duration in schooldays explained most of the associations (64 − 75%) in 4 out 5 HRQOL subscales, except in the association with the HRQOL subscale physical well-being revealing an indirect effect of 71.9%. Conclusions This cross-sectional study described sleep among Norwegian adolescents and demonstrated that sleep durations in weekends and schooldays impact HRQOL and self-efficacy, revealing overall better outcome in HRQOL and self-efficacy with sufficient sleep during schooldays. These findings support the regularity of sleep and highlight the importance of sufficient sleep during schooldays, especially in a school-based sample of adolescents.

Abstract Background Southeast Asia is making tremendous progress towards their 2030 malaria elimination goal but needs new interventions to stop forest malaria. This study trials two new vector control tools, a volatile pyrethroid spatial repellent (VPSR) and insecticide-treated clothing (ITC), amongst forest-exposed populations in Mondulkiri Province Cambodia to inform their potential use for eliminating forest malaria. Methods 21 forest-exposed individuals were given a questionnaire on their perceptions of malaria and preventive practices used, after which they trialed two products sequentially. Clothes was treated with ITC by the study team. Mixed methods were used to understand their experience, attitudes, and preferences regarding the products trialed. Quantitative data was summarized and qualitative insights were analysed using thematic analysis, applying the Capability, Opportunity, and Motivation Behaviour Change (COM-B) model and Behaviour Change Wheel Framework to identify intervention functions to support tailored product rollout amongst these populations. Results Study participants reported a need for protection from mosquito bites in outdoor and forest-exposed settings and perceived both products trialed to be effective for this purpose. The VPSR product was preferred when travel was not required, whereas ITC was preferred for ease of use when going to the forest, especially in rainy conditions. COM-B analysis identified that key enablers for use of both products included their perceived efficacy and ease of use, which required no skill or preparation. For barriers to use, the odour of ITC was sometimes perceived as being toxic, as well as its inability to protect uncovered skin from mosquito bites, while the perceived usefulness of the VPSR product trialed was limited by its water sensitivity in rainy forest settings. Intervention components to encourage appropriate and sustained use of these products include education about how to use these products and what to expect, persuasion to use them from community leaders and targeted channels, and enablement to facilitate convenient and affordable access. Conclusion The rollout of VPSRs and ITC amongst forest-exposed populations can be useful for eliminating malaria in Southeast Asia. Study findings can be applied to increase product uptake among forest exposed populations in Cambodia, while manufacturers can aim to develop products that are rainproof, easy to use in forest settings, and have favourable odour profiles to target users.

It is well known that N-methyl-D-aspartate receptor encephalitis (NMDARE) can be triggered by infectious encephalitis such as herpes simplex virus 1 encephalitis (HSE). However, the incidence of post-HSE NMDARE in Denmark is unknown. We reviewed literature cases and compared these to retrospectively identified cases of post-HSE NMDARE in Denmark, using a national cohort database of autoimmune encephalitis (AE) and two regional databases of infectious encephalitis patients. We identified 80 post-HSE NMDARE cases in the literature, 66% being children, who more often presented movement disorders, decreased consciousness, and sleep disturbances compared to adults. Eight patients with post-HSE NMDARE were identified from the national cohort database of AE, none being children. Forty-four HSE patients were identified from the regional infectious encephalitis databases. Of these, 16 (36%) fulfilled the Graus criteria for probable/definite NMDARE, and eight (18%) presented a prolonged/relapsing disease course. Ten (23%) were tested for AE during hospitalization. Six (14%) had leftover cerebrospinal fluid available for retrospective autoantibody testing. One out of these six patients (17%) harbored NMDARE antibodies. Thus, in total, nine post-HSE NMDARE patients have been identified in Denmark from 2009 to 2021. Comparing the adult Danish patients to the literature, Danish patients were older, but the clinical phenotype and paraclinical findings were similar. Overall, the incidence of adult post-HSE NMDARE in the Region of Southern Denmark was 0.17 per million people per year and only 7% of adult HSE patients in the region were diagnosed with post-HSE NMDARE. Our findings suggest that adult patients are still underdiagnosed and the absence of pediatric cases diagnosed with post-HSE NMDARE in Denmark is highly concerning.

This study investigated the effects of substrates composed of various ratios of wood fiber and peat (0, 25, 50, 75, and 100% peat (v/v)) mixed with different amounts of lime (0, 2, 4, 6, and 8 g L−1) and start fertilizer (0, 2, and 4 g L−1 Multimix) on the growth and biomass accumulation of petunia (Petunia x hybrida Vilm ‘Finity F1 Purple’) and basil (Ocimum basilicum L. ‘Marian’) in an ebb-and-flow greenhouse system. Growth parameters included plant height, weight, canopy diameter, and chlorosis symptoms for petunia, along with substrate pH and EC measurements. Petunia showed optimal growth in substrates with higher peat content, while basil produced satisfactory biomass across a pH range of 5–7 regardless of substrate type. Optimal petunia cultivation in 100% wood fiber required a significant dose of start fertilizer without lime. Monitoring pH and EC using pour-through and press methods revealed a pH decrease in substrates with added start fertilizer, while substrates with higher wood fiber content were less acidic. Substrates with over 50% (v/v) wood fiber without lime showed a rapid pH increase over five weeks. The pour-through method generally underestimated EC values compared to the press method. These findings contribute to optimizing the wood fiber/peat blends for sustainable horticulture.