Probiotic supplementation and risk of necrotizing enterocolitis and mortality among extremely preterm infants-the Probiotics in Extreme Prematurity in Scandinavia (PEPS) trial: study protocol for a multicenter, double-blinded, placebo-controlled, and registry-based randomized controlled trial.

BACKGROUND: Extremely preterm infants, defined as those born before 28 weeks' gestational age, are a very vulnerable patient group at high risk for adverse outcomes, such as necrotizing enterocolitis and death. Necrotizing enterocolitis is an inflammatory gastrointestinal disease with high incidence in this cohort and has severe implications on morbidity and mortality. Previous randomized controlled trials have shown reduced incidence of necrotizing enterocolitis among older preterm infants following probiotic supplementation. However, these trials were underpowered for extremely preterm infants, rendering evidence for probiotic supplementation in this population insufficient to date. METHODS: The Probiotics in Extreme Prematurity in Scandinavia (PEPS) trial is a multicenter, double-blinded, placebo-controlled and registry-based randomized controlled trial conducted among extremely preterm infants (n = 1620) born at six tertiary neonatal units in Sweden and four units in Denmark. Enrolled infants will be allocated to receive either probiotic supplementation with ProPrems® (Bifidobacterium infantis, Bifidobacterium lactis, and Streptococcus thermophilus) diluted in 3 mL breastmilk or placebo (0.5 g maltodextrin powder) diluted in 3 mL breastmilk per day until gestational week 34. The primary composite outcome is incidence of necrotizing enterocolitis and/or mortality. Secondary outcomes include incidence of late-onset sepsis, length of hospitalization, use of antibiotics, feeding tolerance, growth, and body composition at age of full-term and 3 months corrected age after hospital discharge. DISCUSSION: Current recommendations for probiotic supplementation in Sweden and Denmark do not include extremely preterm infants due to lack of evidence in this population. However, this young subgroup is notably the most at risk for experiencing adverse outcomes. This trial aims to investigate the effects of probiotic supplementation on necrotizing enterocolitis, death, and other relevant outcomes to provide sufficiently powered, high-quality evidence to inform probiotic supplementation guidelines in this population. The results could have implications for clinical practice both in Sweden and Denmark and worldwide. TRIAL REGISTRATION: ( Clinicaltrials.gov ): NCT05604846.

The economic burden of diseases in the Nordic countries: A systematic review.

BACKGROUND: Economic burden studies can provide insights into the drivers leading to increasing healthcare costs. It can also provide a more holistic view of how diseases impact the welfare of patients and their families. Having concrete estimates of the economic burden across multiple diseases can help policymakers determine which diseases are economically more burdensome. This study aimed to review and summarise comprehensively economic burden studies across multiple diseases in the Nordic countries between 2000 and 2020. METHODS: According to the 2020 PRISMA statement, a systematic literature review was conducted in PubMed, CINAHL, Academic Search Premier and Global Health databases using key terms related to the economic burden of any disease in Denmark, Finland, Greenland, Iceland, Norway and Sweden. Grey literature was also reviewed. RESULTS: A total of 10,050 potential titles and abstracts were identified and screened, and 254 full-text papers that met the inclusion criteria were evaluated by two independent reviewers. Of these, 119 articles were included in a qualitative synthesis. Twenty-nine had clearly defined comparison groups, thus able to attribute the costs to the disease. Large variations concerning methodology and cost components were noted. Across diseases, the economic burden ranged from EUR 1668 per patient annually for chronic obstructive pulmonary disease to EUR 93,041 for multiple sclerosis. However, estimates varied widely, even within each disease. CONCLUSIONS: Our review highlights the need for more comparable economic burden studies. Future studies should focus on applying robust methodology and homogeneous cost-reporting methods to inform policymakers about which diseases are economically more burdensome.

Maternal intake of folate during pregnancy and risk of cerebral palsy in the MOBAND-CP cohort.

BACKGROUND: Folate prevents neural tube defects and may play a role in some neurodevelopmental disorders. OBJECTIVES: We investigated whether higher intakes of periconceptional or midpregnancy folate, as recommended, were associated with a reduced risk of offspring cerebral palsy (CP). METHODS: We included participants from the Nordic collaboration cohort consisting of mother-child dyads in the Danish National Birth Cohort and the Norwegian Mother, Father, and Child Cohort Study [combined as MOthers and BAbies in Norway and Denmark (MOBAND-CP)]. A total of 190,989 live-born children surviving the first year of life were included. Missing covariate data were multiply imputed. Our exposures were defined as any or no folic acid supplementation in gestational weeks (GWs) -4 to 8 (periconceptional), 9 to 12, and -4 to 12, and supplemental, dietary, and total folate during midpregnancy (GWs 22-25). CP overall and the unilateral and bilateral spastic subtypes, as well as CP with low or moderate/high gross motor function impairments, were our outcomes of interest. RESULTS: Periconceptional folic acid supplementation was not associated with CP [adjusted odds ratio (aOR), 1.02; 95% CI: 0.82-1.28]. However, supplementation in GWs 9 to 12 was associated with a reduced risk of CP (aOR, 0.74; 95% CI: 0.57-0.96), and inverse associations were indicated for both the unilateral (aOR, 0.68; 95% CI: 0.46-1.02) and bilateral (aOR, 0.70; 95% CI: 0.49-1.02) spastic subtypes, although the associations were not statistically significant. Supplemental or dietary folate in midpregnancy alone were not associated with CP. Strong inverse associations were observed with low gross motor function impairment (aOR, 0.49; 95% CI: 0.29-0.83), while for unilateral CP the aOR was 0.63 (95% CI: 0.34-1.22) for intakes of ≥500 compared to ≤199 dietary folate equivalents/day during midpregnancy. CONCLUSIONS: Our findings suggest that folate intakes in GWs 9 to 12 and midpregnancy were associated with lower risks of CP, while no association was observed for periconceptional supplementation.

Historical, archaeological and linguistic evidence test the phylogenetic inference of Viking-Age plant use.

In this paper, past plant knowledge serves as a case study to highlight the promise and challenges of interdisciplinary data collection and interpretation in cultural evolution. Plants are central to human life and yet, apart from the role of major crops, people-plant relations have been marginal to the study of culture. Archaeological, linguistic, and historical evidence are often limited when it comes to studying the past role of plants. This is the case in the Nordic countries, where extensive collections of various plant use records are absent until the 1700s. Here, we test if relatively recent ethnobotanical data can be used to trace back ancient plant knowledge in the Nordic countries. Phylogenetic inferences of ancestral states are evaluated against historical, linguistic, and archaeobotanical evidence. The exercise allows us to discuss the opportunities and shortcomings of using phylogenetic comparative methods to study past botanical knowledge. We propose a 'triangulation method' that not only combines multiple lines of evidence, but also quantitative and qualitative approaches. This article is part of the theme issue 'Foundations of cultural evolution'.

Regulating and Cultural Ecosystem Services of Urban Green Infrastructure in the Nordic Countries: A Systematic Review.

In the Nordic countries (Denmark, Finland, Iceland, Norway and Sweden), the Urban Green Infrastructure (UGI) has been traditionally targeted at reducing flood risk. However, other Ecosystem Services (ES) became increasingly relevant in response to the challenges of urbanization and climate change. In total, 90 scientific articles addressing ES considered crucial contributions to the quality of life in cities are reviewed. These are classified as (1) regulating ES that minimize hazards such as heat, floods, air pollution and noise, and (2) cultural ES that promote well-being and health. We conclude that the planning and design of UGI should balance both the provision of ES and their side effects and disservices, aspects that seem to have been only marginally investigated. Climate-sensitive planning practices are critical to guarantee that seasonal climate variability is accounted for at high-latitude regions. Nevertheless, diverging and seemingly inconsistent findings, together with gaps in the understanding of long-term effects, create obstacles for practitioners. Additionally, the limited involvement of end users points to a need of better engagement and communication, which in overall call for more collaborative research. Close relationships and interactions among different ES provided by urban greenery were found, yet few studies attempted an integrated evaluation. We argue that promoting interdisciplinary studies is fundamental to attain a holistic understanding of how plant traits affect the resulting ES; of the synergies between biophysical, physiological and psychological processes; and of the potential disservices of UGI, specifically in Nordic cities.

Vitamin D status and current policies to achieve adequate vitamin D intake in the Nordic countries.

Aims: Nordic countries share fairly similar food culture and geographical location as well as common nutrition recommendations. The aim of this paper was to review the latest data on vitamin D status and intake and to describe the national supplementation and food fortification policies to achieve adequate vitamin D intake in the Nordic countries. Methods: The data are based on results derived from a literature search presented in a workshop held in Helsinki in November 2018 and completed by recent studies. Results: Vitamin D policies and the implementation of the recommendations differ among the Nordic countries. Vitamin D fortification policies can be mandatory or voluntary and widespread, moderate or non-existent. Vitamin D supplementation recommendations differ, ranging from all age groups being advised to take supplements to only infants. In the general adult population of the Nordic countries, vitamin D status and intake are better than in the risk groups that are not consuming vitamin D supplements or foods containing vitamin D. Non-Western immigrant populations in all Nordic countries share the problem of vitamin D insufficiency and deficiency. Conclusions: Despite the common nutrition recommendations, there are differences between the Nordic countries in the implementation of the recommendations and policies to achieve adequate vitamin D intake and status. There is a need for wider Nordic collaboration studies as well as strategies to improve vitamin D status, especially in risk groups.

A concept analysis of creative activities as intervention in occupational therapy.

Background: This article is based on a common understanding of the concept of creative activities as intervention, as described in occupational therapy literature. Historically, creative activities have been used as intervention in occupational therapy. There is, however, a lack of clarity in descriptions of the concept.Aims/Objectives: To investigate and clarify the concept of creative activities as intervention (CaI) and to validate the findings in occupational therapy practice.Material and methods: A selection of articles according to PRISMA resulted in 15 articles, analysed with concept analysis. The results were validated by a reference panel of seven occupational therapists using a questionnaire and data was analysed by descriptive statistics.Results: Five attributes defined CaI: (1) Often consisting of elements of art and craft using mind and body, (2) Being experienced as meaningful, (3) Creating creative processes, (4) Developing skills, enhancing occupational performance and managing everyday life, and (5) Being easy to modify individually or in groups with different approaches. Three cases were generated from the attributes to illustrate the integrity of the analysis.Conclusions and significance: The results led to a description of CaI that could facilitate future research communication and common definition in occupational therapy practice.

Comparing nutrient reference concentrations in Nordic countries with focus on lowland rivers.

Reference conditions of water bodies are defined as the natural or minimal anthropogenically disturbed state. We compared the methods for determining total phosphorus and total nitrogen concentrations in rivers in Finland, Norway and Sweden as well as the established reference conditions and evaluated the possibility for transfer and harmonisation of methods. We found that both methods and values differed, especially for lowland rivers with a high proportion of agriculture in the catchment. Since Denmark has not yet set reference conditions for rivers, two of the Nordic methods were tested for Danish conditions. We conclude that some of the established methods are promising but that further development is required. We moreover argue that harmonisation of reference conditions is needed to obtain common benchmarks for assessing the impacts of current and future land use changes on water quality.

The Neolithic Pitted Ware culture foragers were culturally but not genetically influenced by the Battle Axe culture herders.

OBJECTIVES: In order to understand contacts between cultural spheres in the third millennium BC, we investigated the impact of a new herder culture, the Battle Axe culture, arriving to Scandinavia on the people of the sub-Neolithic hunter-gatherer Pitted Ware culture. By investigating the genetic make-up of Pitted Ware culture people from two types of burials (typical Pitted Ware culture burials and Battle Axe culture-influenced burials), we could determine the impact of migration and the impact of cultural influences. METHODS: We sequenced and analyzed the genomes of 25 individuals from typical Pitted Ware culture burials and from Pitted Ware culture burials with Battle Axe culture influences in order to determine if the different burial types were associated with different gene-pools. RESULTS: The genomic data show that all individuals belonged to one genetic population-a population associated with the Pitted Ware culture-irrespective of the burial style. CONCLUSION: We conclude that the Pitted Ware culture communities were not impacted by gene-flow, that is, via migration or exchange of mates. These different cultural expressions in the Pitted Ware culture burials are instead a consequence of cultural exchange.

Marine resource abundance drove pre-agricultural population increase in Stone Age Scandinavia.

How climate and ecology affect key cultural transformations remains debated in the context of long-term socio-cultural development because of spatially and temporally disjunct climate and archaeological records. The introduction of agriculture triggered a major population increase across Europe. However, in Southern Scandinavia it was preceded by ~500 years of sustained population growth. Here we show that this growth was driven by long-term enhanced marine production conditioned by the Holocene Thermal Maximum, a time of elevated temperature, sea level and salinity across coastal waters. We identify two periods of increased marine production across trophic levels (P1 7600-7100 and P2 6400-5900 cal. yr BP) that coincide with markedly increased mollusc collection and accumulation of shell middens, indicating greater marine resource availability. Between ~7600-5900 BP, intense exploitation of a warmer, more productive marine environment by Mesolithic hunter-gatherers drove cultural development, including maritime technological innovation, and from ca. 6400-5900 BP, underpinned a ~four-fold human population growth.

Health effects of nutrients and environmental pollutants in Baltic herring and salmon: a quantitative benefit-risk assessment.

BACKGROUND: Health risks linked with dioxin in fish remain a complex policy issue. Fatty Baltic fish contain persistent pollutants, but they are otherwise healthy food. We studied the health benefits and risks associated with Baltic herring and salmon in four countries to identify critical uncertainties and to facilitate an evidence-based discussion. METHODS: We performed an online survey investigating consumers' fish consumption and its motivation in Denmark, Estonia, Finland, and Sweden. Dioxin and methylmercury concentrations were estimated based on Finnish studies. Exposure-response functions for several health endpoints were evaluated and quantified based on the scientific literature. We also quantified the infertility risk of men based on a recent European risk assessment estimating childhood dioxin exposure and its effect on sperm concentration later in life. RESULTS: Baltic herring and salmon contain omega-3 fatty acids and vitamin D, and the beneficial impact of these fishes on cardiovascular diseases, mortality, and the risk of depression and cancer clearly outweighs risks of dioxins and methylmercury in people older than 45 years of age and in young men. Young women may expose their children to pollutants during pregnancy and breast feeding. This study suggests that even in this critical subgroup, the risks are small and the health benefits are greater than or at least similar to the health risks. Value of information analysis demonstrated that the remaining scientific uncertainties are not large. In contrast, there are several critical uncertainties that are inherently value judgements, such as whether exceeding the tolerable weekly intake is an adverse outcome as such; and whether or not subgroup-specific restrictions are problematic. CONCLUSIONS: The potential health risks attributable to dioxins in Baltic fish have more than halved in the past 10 years. The new risk assessment issued by the European Food Safety Authority clearly increases the fraction of the population exceeding the tolerable dioxin intake, but nonetheless, quantitative estimates of net health impacts change only marginally. Increased use of small herring (which have less pollutants) is a no-regret option. A more relevant value-based policy discussion rather than research is needed to clarify official recommendations related to dioxins in fish.

Scandinavian research on complementary and alternative medicine: A bibliometric study.

Aim: The aim of this study is to analyse the development of Scandinavian research on complementary and alternative medicine in terms of publication pattern and general content. Furthermore we will map research networks. Methods and data: This study is based on bibliometric methods. The dataset consists of 1441 publications with at least one author with a Scandinavian address and/or organisational affiliation, from 2005-2017, in Medline and Web of Science. Results and conclusions: Complementary and alternative medicine is a small and moderately growing research field in Scandinavia, with an average of 120 publications per year. The largest sub-term is integrative and complementary medicine, but the majority of documents are classified as other medical sub-fields. A similar pattern is found regarding the sources. The Medical Subject Heading classifications of the documents and the author keywords indicate that much of the relevant research takes a general focus on complementary and alternative medicine. Regarding specific therapies, mind-body and sensory art therapies are particularly prominent in the material. Various aspects of pain, mental health and gynaecology are recurrent health issues. In total, 31.5% of the publications are classified as clinical trials. The organisations referenced most frequently in the material are Karolinska Institutet and UiT Tromsö and it is clear the research is based at large universities and university hospitals. The research networks have relatively different profiles and collaborate with both Scandinavian and international organisations.

The genomic ancestry of the Scandinavian Battle Axe Culture people and their relation to the broader Corded Ware horizon.

The Neolithic period is characterized by major cultural transformations and human migrations, with lasting effects across Europe. To understand the population dynamics in Neolithic Scandinavia and the Baltic Sea area, we investigate the genomes of individuals associated with the Battle Axe Culture (BAC), a Middle Neolithic complex in Scandinavia resembling the continental Corded Ware Culture (CWC). We sequenced 11 individuals (dated to 3330-1665 calibrated before common era (cal BCE)) from modern-day Sweden, Estonia, and Poland to 0.26-3.24× coverage. Three of the individuals were from CWC contexts and two from the central-Swedish BAC burial 'Bergsgraven'. By analysing these genomes together with the previously published data, we show that the BAC represents a group different from other Neolithic populations in Scandinavia, revealing stratification among cultural groups. Similar to continental CWC, the BAC-associated individuals display ancestry from the Pontic-Caspian steppe herders, as well as smaller components originating from hunter-gatherers and Early Neolithic farmers. Thus, the steppe ancestry seen in these Scandinavian BAC individuals can be explained only by migration into Scandinavia. Furthermore, we highlight the reuse of megalithic tombs of the earlier Funnel Beaker Culture (FBC) by people related to BAC. The BAC groups likely mixed with resident middle Neolithic farmers (e.g. FBC) without substantial contributions from Neolithic foragers.

Dietary Patterns and Cardiometabolic Outcomes in Diabetes: A Summary of Systematic Reviews and Meta-Analyses.

The Diabetes and Nutrition Study Group (DNSG) of the European Association for the Study of Diabetes (EASD) conducted a review of existing systematic reviews and meta-analyses to explain the relationship between different dietary patterns and patient-important cardiometabolic outcomes. To update the clinical practice guidelines for nutrition therapy in the prevention and management of diabetes, we summarize the evidence from these evidence syntheses for the Mediterranean, Dietary Approaches to Stop Hypertension (DASH), Portfolio, Nordic, liquid meal replacement, and vegetarian dietary patterns. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of evidence. We summarized the evidence for disease incidence outcomes and risk factor outcomes using risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs), respectively. The Mediterranean diet showed a cardiovascular disease (CVD) incidence (RR: 0.62; 95%CI, 0.50, 0.78), and non-significant CVD mortality (RR: 0.67; 95%CI, 0.45, 1.00) benefit. The DASH dietary pattern improved cardiometabolic risk factors (P < 0.05) and was associated with the decreased incidence of CVD (RR, 0.80; 95%CI, 0.76, 0.85). Vegetarian dietary patterns were associated with improved cardiometabolic risk factors (P < 0.05) and the reduced incidence (0.72; 95%CI: 0.61, 0.85) and mortality (RR, 0.78; 95%CI, 0.69, 0.88) of coronary heart disease. The Portfolio dietary pattern improved cardiometabolic risk factors and reduced estimated 10-year coronary heart disease (CHD) risk by 13% (-1.34% (95%CI, -2.19 to -0.49)). The Nordic dietary pattern was correlated with decreased CVD (0.93 (95%CI, 0.88, 0.99)) and stroke incidence (0.87 (95%CI, 0.77, 0.97)) and, along with liquid meal replacements, improved cardiometabolic risk factors (P < 0.05). The evidence was assessed as low to moderate certainty for most dietary patterns and outcome pairs. Current evidence suggests that the Mediterranean, DASH, Portfolio, Nordic, liquid meal replacement and vegetarian dietary patterns have cardiometabolic advantages in populations inclusive of diabetes.

Radiation-induced cystitis treated with hyperbaric oxygen therapy (RICH-ART): a randomised, controlled, phase 2-3 trial.

BACKGROUND: Late radiation cystitis is an adverse effect of cancer treatment with radiotherapy in the pelvic region. Symptoms of late radiation cystitis can be assessed with the Expanded Prostate Index Composite Score (EPIC). Previous reports indicate that hyperbaric oxygen therapy reduces symptoms from late radiation cystitis, but the evidence is predominantly based on non-randomised and retrospective studies. We aimed to assess whether hyperbaric oxygen therapy would mitigate symptoms of late radiation cystitis. METHODS: We did a randomised, controlled, phase 2-3 trial (RICH-ART [Radiation Induced Cystitis treated with Hyperbaric oxygen-A Randomised controlled Trial]) at five Nordic university hospitals. All patients aged 18-80 years, with pelvic radiotherapy completed at least 6 months previously, a score of less than 80 in the urinary domain of the Expanded Prostate Index Composite Score (EPIC), and referred to participating hyperbaric clinics due to symptoms of late radiation cystitis, were eligible for inclusion. Exclusion criteria were ongoing bleeding requiring blood transfusion exceeding 500 mL in the past 4 weeks, permanent urinary catheter, bladder capacity less than 100 mL, fistula in the urinary bladder, previous treatment with hyperbaric oxygen therapy for late radiation injuries, and contraindications to hyperbaric oxygen therapy. After computer-generated 1:1 randomisation with block sizes of four for each stratification group (sex, time from radiotherapy to inclusion, and previous invasive surgery in the pelvic area), patients received hyperbaric oxygen therapy (30-40 sessions, 100% oxygen, breathed at a pressure of 240-250 kPa, for 80-90 min daily) or standard care with no restrictions for other medications or interventions. No masking was applied. The primary outcome was change in patient-perceived urinary symptoms assessed with EPIC from inclusion to follow-up at visit 4 (6-8 months later), measured as absolute change in EPIC urinary total score. RICH-ART closed enrolment on Dec 31, 2017; the last follow-up data will be compiled in 2023. RICH-ART is registered with ClinicalTrials.gov, number NCT01659723, and with the European Medicines Agency, number EudraCT 2012-001381-15. FINDINGS: Of 223 patients screened between May 9, 2012, and Dec 20, 2017, 87 patients were enrolled and randomly assigned to either hyperbaric oxygen therapy (n=42) or standard care (n=45). After excluding eight patients who withdrew consent directly after randomisation (one in the hyperbaric oxygen therapy group and seven in the standard care group), 79 were included in the intention-to-treat analyses (n=41 in the hyperbaric oxygen therapy group, n=38 in the standard care group). Median time from randomisation to visit 4 was 234 days (IQR 210-262) in the hyperbaric oxygen therapy group and 217 days (195-237) in the standard care group. The difference between change in group mean of EPIC urinary total score at visit 4 was 10·1 points (95% CI 2·2-18·1; p=0·013; 17·8 points [SD 18·4] in the hyperbaric oxygen therapy group vs 7·7 points [15·5] in the standard care group). 17 (41%) of 41 patients in the hyperbaric oxygen therapy group experienced transient grade 1-2 adverse events, related to sight and hearing, during the period of hyperbaric oxygen therapy. INTERPRETATION: Our results suggest that hyperbaric oxygen therapy relieves symptoms of late radiation cystitis. We conclude that hyperbaric oxygen therapy is a safe and well tolerated treatment. FUNDING: The regional research fund of Region Västra Götaland, Sweden, the regional Health Technology Assessment Centre at Sahlgrenska University Hospital, Sweden, and Lions Cancer Research Fund of Western Sweden.

Sagas of the Solanaceae: Speculative ethnobotanical perspectives on the Norse berserkers.

ETHNOPHARMACOLOGICAL RELEVANCE: The Norse berserkers were wild warriors of Scandinavia known to enter a trance-like state that allowed them to fight with increased strength and a rage that granted them immunity to many forms of harm in battle. Though many theories have been advanced as to the cause of this state, the most widely believed is that the intoxicating mushroom Amanita muscaria was used. AIM OF THE STUDY: The following article underlines the issues with this theory and provides an alternate intoxicant that fits with the reports of berserker behaviour much better: Hyoscyamus niger. MATERIALS AND METHODS: Literature from a variety of disciplines pertaining to history, toxicology, pharmacology, and botany was compiled to frame and support the argument. RESULTS: H. niger proved to be a more likely intoxicant used to induce the berserker rage state. CONCLUSIONS: With its anticholinergic tropane alkaloids and symptom profile, H. niger is a much more likely cause of the berserker state than A muscaria. Though there is not enough archaeological and historical evidence to prove or disprove this theory, it provides a novel explanation that is at present the most viable means of understanding the berserkers' trance.