The Danish national haemoglobinopathy screening programme: Report from 16 years of screening in a low-prevalence, non-endemic region.

The Danish national haemoglobinopathy screening programme seeks to determine parental haemoglobinopathy carrier state antenatally. In this retrospective register-based study, we evaluated the 16-year trajectory of this programme, utilising the Danish Red Blood Cell Centre's laboratory database, covering approximately 77% of the Danish population. During the study period, we observed a substantial increase in annual diagnostic examinations performed, from 389 in 2007 to 3030 in 2022. Women constituted 88% of these cases, aligning with the emphasis of the screening programme. Of these, 54% of women of reproductive age (15-40 years) and 10% of women >40 years were specified as pregnant. During our study period, 61 children were born with a severe haemoglobinopathy, out of which 23 children were born from mothers not residing in Denmark during their first trimester thus not included in the screening programme. Prenatal invasive testing was performed for 60 fetuses, identifying 12 with homozygous or compound heterozygous haemoglobinopathy. The Danish haemoglobinopathy screening programme has provided screening, information and reproductive choices for numerous families. During the study period, screening for haemoglobinopathies has been steadily increasing and is expected to continue to increase. Awareness of and adherence to the screening programme is subject of further investigation and optimisation.

Treatment-related mortality among children with cancer in Denmark during 2001-2021.

BACKGROUND: Survival of children with cancer has markedly improved over recent decades, largely due to intensified treatment regimes. The intensive treatment may, however, result in fatal complications. In this retrospective cohort study, we assessed temporal variation in the incidence of treatment-related death and associated risk factors among children diagnosed with cancer in Denmark during 2001-2021. METHOD: Among all children diagnosed with first incident cancer before age 15 years recorded in the Danish Childhood Cancer Register (n = 3,255), we estimated cumulative incidence of treatment-related death (death in the absence of progressive cancer) within 5 years from diagnosis using Aalen-Johansen estimators and assessed associated risk factors using Cox regression. RESULTS: Among all 3,255 children with cancer, 93 (20% of all 459 deaths) died from treatment. Of these treatment-related deaths, 39 (42%) occurred within 3 months of diagnosis. The 5-year cumulative incidences of treatment-related death were 3.3% during 2001-2010 and 2.5% during 2011-2021 (p = 0.20). During 2011-2021, treatment-related deaths accounted for more than half of all deaths among children with haematological cancers. Risk factors varied according to cancer group and included female sex, age below 1 year at diagnosis, disease relapse, stem cell transplantation, central nervous system involvement, and metastasis at diagnosis. INTERPRETATION: Despite increasing treatment intensities, the incidence of treatment-related death has remained stable during the past 20 years in Denmark. Still, clinical attention is warranted to prevent treatment-related deaths, particularly among children with haematological cancers. Patient characteristics associated with increased treatment-related death risk support patient-specific treatment approaches to avoid these fatalities.

The experiences of grandparents involved in the home-based end-of-life care of their grandchild with cancer: A qualitative secondary data analysis.

While grandparents are often a valuable resource in home-based pediatric end-of-life care, they may also experience psychological consequences when faced with their grandchild's illness and death. In this qualitative study, we performed semi-structured interviews with seven bereaved grandparents of four children with cancer who received home-based end-of-life care and died at home at age <18. Through qualitative content analysis we identified the overarching theme: "Navigating complex and unclear roles to support the family" and five themes: (1) Providing comfort and support; (2) Balancing and adapting involvement; (3) Worrying silently; (4) Managing difficult emotions; and (5) Calling for support and understanding. The findings underline the often conflicting roles that grandparents undertake of providing support while respecting parents' autonomy and putting aside their own emotional reactions. Involving grandparents in pediatric end-of-life care may enhance family resources, but should also consider grandparents' perspectives and need for support.

Assessment and Comparison of Microplastic Contamination in Atlantic Navigation Routes with Known Uncertainty.

Microplastics (MP) have been found in various environments worldwide. However, not many studies focus on the open ocean due to logistical restraints. Between January and May 2020, the NRP Sagres sampled 123 linear paths of subsurface water of the Atlantic Ocean, passing by Cape Verde, the east coast of South America, and the west coast of Africa. The water was sampled through the ship's water system. The membranes were analyzed by the Hydrographic Institute of Portugal and the Norwegian Institute for Water Research by micro-FTIR. The contamination levels were reported with uncertainty, for 99% confidence level (CL), normalized for filtered water volume and the distance traveled during sampling. Uncertainties were calculated through a detailed ″bottom-up″ evaluation. MP were found in about a third of the stations (48 out of 123), and most of those stations (43 out of 48) presented concentrations below 1 m-3 km-1. The sites where higher concentrations were registered were the port of the island of Santiago (Cape Verde) ((5.9 ± 5.2) m-3 km-1), the Guanabara Bay in Rio de Janeiro (Brazil) ((41 ± 27) m-3 km-1), and close to South Africa ((4.9 ± 2.4) m-3 km-1). Most MP found were polyamide, polyester, polyethylene, ethylene vinyl acetate, and poly(methyl methacrylate). The estimated contamination levels cannot be directly compared with information obtained in other studies due to differences in how MP were determined and the unknown uncertainty of their measured values. This article presents a relevant and reliable contribution to understanding the MP distribution in the Atlantic Ocean.

Intersectoral collaboration in home-based end-of-life pediatric cancer care: A qualitative multiple-case study integrating families' and professionals' experiences.

BACKGROUND: Many children and adolescents with incurable cancer and their families prefer to receive end-of-life care and to die at home. This implies a transition of care from hospital to home and presupposes the establishment of a well-functioning collaboration between the family and professionals across health care sectors. AIM: To identify and explore key elements of home-based end-of-life care collaboration for children with cancer, as experienced by their parents and grandparents and the hospital- and community-based professionals involved. DESIGN: Descriptive qualitative multiple-case study. Data were collected by semi-structured interviews and written responses to open-ended questions, and analyzed inductively across cases using qualitative content analysis. SETTING/PARTICIPANTS: Cases comprised a criterion sample of five children (aged <18 years), who died of cancer at home. Cases were represented by the children's bereaved parents (n = 8) and grandparents (n = 7), and community-based professionals (n = 16). Also, hospital-based professionals (n = 10) were interviewed about the children's end-of-life care through group interviews. RESULTS: We identified five main themes, describing key elements of the end-of-life collaboration: Establishing the collaboration, Bolstering family life, Elucidating organization and integration, Managing challenges, and Closing the collaboration. These themes all came under the overarching theme: A mutual trust-based collaboration. On this basis, we developed the "Home-Based Pediatric End-of-Life Care Model for Children with Cancer." CONCLUSIONS: By highlighting key elements in the family-centered, intersectoral and interprofessional end-of-life care collaboration, our "Home-Based Pediatric End-of-Life Care Model for Children with Cancer" offers a framework for further optimization of home-based end-of-life care services for children with cancer and their families.

Inequality in place-of-death among children: a Danish nationwide study.

To identify predictors for home death among children using socio-demographic factors and cause of death. It is a nationwide registry study. A cohort of children (1-17 years) who died between 1 January 2006 and 31 December 2016. It was set in Denmark, Europe. Predictors for home death were assessed: age, gender, diagnosis, region of residence, urbanicity, household income and immigrant status. Of 938 deceased children included, causes of death were solid tumours (17.3%), haematological cancers (8.5%) and non-cancerous conditions (74.2%). A total of 25% died at home. Compared to the lowest quartile, the groups with higher household income did not have a higher probability of dying at home (adjusted odds ratio (adj-OR) 0.8 (95% CI 0.5-1.2/1.3)). Dying of haematological cancers (adj-OR 0.3 (95% CI 0.2-0.7)) and non-cancerous conditions (adj-OR 0.5 (95% CI 0.3-0.7)) was associated with lower odds for home death compared to dying of solid tumours. However, being an immigrant was negatively associated with home death (adj-OR 0.6 (95% CI 0.4-0.9)). Moreover, a tendency was also found that being older, male, living outside the capital and in more urban areas were notable in relation to home death, however, not statistically significant.Conclusions: The fact that household income was not associated with dying at home may be explained by the Danish tax-financed healthcare system. However, having haematological cancers, non-cancerous conditions or being an immigrant were associated with lower odds for home death. Cultural differences along with heterogeneous trajectories may partly explain these differences, which should be considered prospectively. What is Known: • Prior studies have shown disparities in place-of-death of terminally ill children with diagnosis, ethnicity and socio-economic position as key factors. • Danish healthcare is tax-financed and in principle access to healthcare is equal; however, disparities have been found in the intensity of treatment of terminally ill children. What is New: • In a tax-financed, equal-access healthcare system, children died just as frequently at home in families with low as high household income. • Disparities in home death were related to diagnosis and immigrant status.

Interlinkage Between Persistent Organic Pollutants and Plastic in the Waste Management System of India: An Overview.

Improper handling of plastic waste and related chemical pollution has garnered much attention in recent years owing to the associated detrimental impacts on human health and the environment. This article reports an overview of the main interlinkages between persistent organic pollutants (POPs) and plastic in the waste management system of India. Both plastics and POPs share certain common traits such as persistence, resistance to biological degradation, and the ability to get transported over long distances. Throughout the processes of production, consumption, and disposal, plastics interact with and accumulate POPs through several mechanisms and end up co-existing in the environment. Plastic waste can undergo long-range transport through rivers and the oceans, break down into microplastics and get transported through the air, or remain locked in waste dump yards and landfills. Over time, environmental processes lead to the leaching and release of accumulated POPs from these plastic wastes. Plastic recycling in the Indian informal sector including smelting, scrubbing, and shredding of plastic waste, is also a potential major POPs source that demands further investigation. The presence of POPs in plastic waste and their fate in the plastic recycling process have not yet been elucidated. By enhancing our understanding of these processes, this paper may aid policy decisions to combat the release of POPs from different waste types and processes in India.

Laboratory Monitoring of Mother, Fetus, and Newborn in Hemolytic Disease of Fetus and Newborn.

BACKGROUND: Laboratory monitoring of mother, fetus, and newborn in hemolytic disease of fetus and newborn (HDFN) aims to guide clinicians and the immunized women to focus on the most serious problems of alloimmunization and thus minimize the consequences of HDFN in general and of anti-D in particular. Here, we present the current approach of laboratory screening and testing for prevention and monitoring of HDFN at the Copenhagen University Hospital in Denmark. SUMMARY: All pregnant women are typed and screened in the 1st trimester. This serves to identify the RhD-negative pregnant women who at gestational age (GA) of 25 weeks are offered a second screen test and a non-invasive fetal RhD prediction. At GA 29 weeks, and again after delivery, non-immunized RhD-negative women carrying an RhD-positive fetus are offered Rh immunoglobulin. If the 1st trimester screen reveals an alloantibody, antenatal investigation is initiated. This also includes RhD-positive women with alloantibodies. Specificity and titer are determined, the fetal phenotype is predicted by non-invasive genotyping based on cell-free DNA (RhD, K, Rhc, RhC, RhE, ABO), and serial monitoring of titer commences. Based on titers and specificity, monitoring with serial peak systolic velocity measurements in the fetal middle cerebral artery to detect anemia will take place. Intrauterine transfusion is given when fetal anemia is suspected. Monitoring of the newborn by titer and survival of fetal red blood cells by flow cytometry will help predict the length of the recovery of the newborn.

Validation of a Method for Extracting Microplastics from Complex, Organic-Rich, Environmental Matrices.

Complex and organic-rich solid substrates such as sludge and soil have been shown to be contaminated by microplastics; however, methods for extracting plastic particles have not yet been systemically tested or standardized. This study investigated four main protocols for the removal of organic material during analysis of microplastics from complex solid matrices: oxidation using H2O2, Fenton's reagent, and alkaline digestion with NaOH and KOH. Eight common polymer types were used to assess the influence of reagent exposure on particle integrity. Organic matter removal efficiencies were established for test sludge and soil samples. Fenton's reagent was identified as the optimum protocol. All other methods showed signs of particle degradation or resulted in an insufficient reduction in organic matter content. A further validation procedure revealed high microplastic extraction efficiencies for particles with different morphologies. This confirmed the suitability of Fenton's reagent for use in conjunction with density separation for extracting microplastics. This approach affords greater comparability with existing studies that utilize a density-based technique. Recommendations for further method optimization were also identified to improve the recovery of microplastic from complex, organic-rich environmental samples.

All-cause mortality rates and home deaths decreased in children with life-limiting diagnoses in Denmark between 1994 and 2014.

AIM: Specialised paediatric palliative care has not previously been a priority in Denmark. The aim of this study was to support its development and organisation, by examining why and where children died using official national data for 1994-2014. METHODS: We obtained data on 9462 children who died before the age of 18 from the Danish Register of Causes of Death. The causes of deaths were listed according to the codes in the International Classification of Diseases. RESULTS: The all-cause mortality rate decreased by 52% over the study period, and infants below one year accounted for 61% of all deaths. The decline in infant mortality (26%) primarily reflected fewer deaths due to congenital malformations and chromosomal abnormalities (68%) and perinatal deaths (30%). In children aged one year to 17 years, the substantial decrease (65%) was due to external causes (75%) and neoplasms (57%). The relative proportion of hospital deaths increased, while home deaths decreased. CONCLUSION: All-cause mortality rate decreased markedly, and the relative proportion of hospital deaths increased. The results may reflect more aggressive and effective treatment attempts to save lives, but some terminally ill children may be deprived of the option of dying at home.

False positivity of ETV6/RUNX1 detected by FISH in healthy newborns and adults.

The leukemia-associated ETV6-RUNX1-translocation frequently emerges prenatally. Reverse-transcriptase PCR screening may indicate presence of ETV6-RUNX1 transcripts in random cord blood samples. Subsequent cell enrichment validation finds significantly lower levels than validation applying fluorescence in situ hybridization (FISH) (<10(-5) vs. 10(-3) to 10(-4)). Using three FISH probe sets, we screened 179,000 cells from ETV6-RUNX1-positive dilution series, healthy adults and random cord blood samples. The t(12;21) single fusion extra signal translocation probe and the ETV6 break apart probe gave false positive results mimicking ETV6-RUNX1-positive cell levels of 10(-3). This questions the paradigm that 1% of newborns have ETV6-RUNX1-positive cells at levels of 10(-3) to 10(-4).

Inflammatory markers in umbilical cord blood from small-for-gestational-age newborns.

This study investigates the role of inflammation in intrauterine growth retardation by exploring the levels of inflammatory markers in umbilical cord blood from neonates who were born small-for-gestational-age (SGA) and comparing them to neonates who were born appropriate-for-gestational-age (AGA). Interleukin 6 (IL-6), Tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) were measured by standard methods in term or near-term (gestational age >36 weeks) neonates born SGA (n = 45) and a matched group of neonates born AGA (n = 45). Infants exposed to maternal chronic diseases, diabetes or pre-eclampsia were excluded. SGA was defined as two standard derivations below the expected for term and gender. In multivariate regression analyses significant elevation in cord blood concentration of IL-6 was demonstrated in the SGA group (mean 4.56 vs. 2.38, p = 0.002). The results indicate the presence of elevated inflammatory markers in the cord blood from SGA infants compared to AGA infants, and consequently the results suggest an inflammatory component in intrauterine growth restriction (IUGR).

Developing professional competence in an unfamiliar setting: Practice learning in Zambia.

BACKGROUND: Higher education needs to provide students with competencies to meet the health and social needs of a society characterised by increased globalisation and diversity. Occupational therapy students from Norway expressed that learning experiences outside their comfort zone within Zambian placements, have had a profound impact on their professional competence. AIMS AND OBJECTIVES: Enhanced understanding of how learning experiences in international placement impact on students' professional competence. MATERIAL AND METHODS: Focus group interviews with three cohorts of students were analysed using thematic cross-case analysis integrated with an iterative reflexive process. Transformative learning was used as a theoretical framework for this analysis. RESULTS: Three themes emerged from the analysis; 1) Feelings of uncertainty and emotional distress; 2) Drawing on available resources to meet the challenges; 3) Handling challenges promote professional competence. CONCLUSION: Learning experiences significant for developing professional competence goes beyond students' habitual practice and previous mindset. Students develop generic skills, such as tolerance, flexibility, creativity, awareness of sustainability and professional confidence. SIGNIFICANCE: New and more appropriate understandings of students' placement experiences leading to more adequate and relevant strategies, are in consistence with skills required for twenty first century occupational therapy practice.

Paediatric end-of-life care - symptoms and problems: parent assessment.

OBJECTIVE: Symptoms and problems (S&P) are under-reported in children in end-of-life care.To target future interventions, the primary aim was to examine S&P in children in end-of-life care. METHODS: All parents, who lost a child under the age of 18 years due to life-limiting diagnoses in the period 2012-2014 in Denmark, were invited to complete a self-administered questionnaire in 2017. In all, 152 (38%) children were represented by 136 mothers and 57 fathers. In the present study, parents' assessments of S&P during the last month of life were restricted to children aged 3-18 years. Data were analyses by means of descriptive statistics. RESULTS: Children ≥3 years at the time of death were represented by 71 parents (48 mothers and 23 fathers) representing 56 out of the 152 children. Physical fatigue (93%), sleepiness (90%), poor appetite (87%), pain (84%) and nausea (84%) were the five most frequent symptoms reported by the parents. In all, 65% of the parents reported that satisfactory pain relief was obtained and 64% of the parents reported that the healthcare services to a large extent reacted quickly, when the child and/or family needed help. However, 46% of the parents experienced 'mess-ups' or sloppy services in the primary ward and 27% experienced that the children suffered from fear of death. CONCLUSION: According to the parents, children with life-limiting diagnosis are highly symptomatic and have substantial problems during end-of-life care. Our findings indicate that systematic screening of S&P in children should be considered.

Home-Based Specialized Pediatric Palliative Care: A Systematic Review and Meta-Analysis.

CONTEXT: Although specialized pediatric palliative care (SPPC) teams increasingly provide home-based care, the evidence of its impact has not yet been systematically evaluated. OBJECTIVES: To examine the impact of home-based SPPC in children and adolescents with life-limiting conditions, regarding place of death, quality of life and symptom burden. METHODS: We searched Medline, EMBASE, CINAHL, PsycINFO, the Cochrane Central Register of Controlled Trials, Web of Science and Scopus for studies comparing children and adolescents with life-limiting conditions receiving home-based SPPC with children and adolescents not receiving home-based SPPC, or studies reporting before-and-after measurements. We included studies that reported on place of death, quality of life and/or symptoms. Two authors independently screened the articles, extracted data, and assessed quality. Results were synthesized as a systematic narrative synthesis and meta-analysis, using a random-effects model. RESULTS: We included five studies, which reported on 392 children and adolescents. Meta-analysis showed that receiving home-based SPPC was associated with a more than fourfold increased likelihood of home death (risk ratio 4.64, 95% confidence interval 3.06-7.04; 3 studies; n=296). Most studies reported improved quality of life and reduced symptom burden. The included studies were of low to moderate quality with a high risk of bias. CONCLUSION: This systematic review suggests that home-based SPPC is associated with increased likelihood of home death, and might be associated with improved quality of life and reduced symptom burden. The small number of studies and an overall high risk of bias, however, makes the overall strength of evidence low.

Measuring riverine macroplastic: Methods, harmonisation, and quality control.

River systems are a key environmental recipient of macroplastic pollution. Understanding the sources of macroplastic to rivers and the mechanisms controlling fate and transport is essential to identify and tailor measures that can effectively reduce global plastic pollution. Several guidelines exist for monitoring macroplastic in rivers; yet, no single method has emerged representing the standard approach. This reflects the substantial variability in river systems globally and the need to adapt methods to the local environmental context and monitoring goals. Here we present a critical review of methods used to measure macroplastic flows in rivers, with a specific focus on opportunities for methods testing, harmonisation, and quality assurance and quality control (QA/QC). Several studies have already revealed important findings; however, there is significant disparity in the reporting of methodologies and data. There is a need to converge methods, and their adaptations, towards greater comparability. This can be achieved through: i) methods testing to better understand what each method effectively measures and how it can be applied in different contexts; ii) incorporating QA/QC procedures during sampling and analysis; and iii) reporting methodological details and data in a more harmonised way to facilitate comparability and the utilisation of data by several end users, including policy makers. Setting this as a priority now will facilitate the collection of rigorous and comparable monitoring data to help frame solutions to limit plastic pollution, including the forthcoming global treaty on plastic pollution.

RT-PCR screening for ETV6-RUNX1-positive clones in cord blood from newborns in the Danish National Birth Cohort.

BACKGROUND: Several large biobanks comprising umbilical cord blood samples have been established allowing efforts to characterize the prevalence and risk factors for preleukemic cell clones in healthy newborns. This study explores the feasibility of demonstrating translocation ETV6-RUNX1 transcripts by reverse transcription polymerase chain reaction in newborns enrolled in a large Danish National Birth Cohort. CONCLUSIONS: The study emphasizes the necessity of either storing viable cord blood cells or preparation of the RNA within 1 to 2 days of birth, in large scale studies of the natural history of childhood acute lymphoblastic leukemia. Finally, the estimated frequency of translocation ETV6-RUNX1-positive cells was below 10.

End-of-life communication: a nationwide study of bereaved parents' perceptions.

OBJECTIVE: To investigate bereaved parents' perception of end-of-life communication with healthcare professionals after losing a child due to life-limiting diagnoses. METHODS: A national register identified the causes of death of 951 children aged 0-18 years during the period 2012-2014. A previously described classification of life-limiting diagnoses identified 402 children. A modified version of the self-administered questionnaire 'To Lose a Child' was distributed to the parents of these 402 children, capturing their perceptions of communication with the healthcare professionals throughout the child's disease trajectory and imminent death. RESULTS: A total of 193 bereaved parents, representing 38% of the identified children, participated in the study. Overall, 98% of the parents expressed the view that physicians should immediately disclose when curatively intended treatment options were exhausted. Some 79% of parents reported that information about their child's incurable illness was given in an appropriate manner; however, 42% said that information about the child's imminent death was given too late. Finally, 31% felt deprived of the option to say goodbye to their child in their preferred manner, and 56% said that their child's death was "a shock". CONCLUSIONS: Parents request accurate and timely information. However, a substantial number of the parents surveyed reported that healthcare professionals communicated too late about palliative care and end-of-life issues. Even though healthcare professionals strive to communicate effectively with dying children and their parents, barriers were identified that may hinder even the best of intentions. National guidelines addressing communication issues and improved education of healthcare professionals should form part of any future agenda.

Moving forward in microplastic research: A Norwegian perspective.

Given the increasing attention on the occurrence of microplastics in the environment, and the potential environmental threats they pose, there is a need for researchers to move quickly from basic understanding to applied science that supports decision makers in finding feasible mitigation measures and solutions. At the same time, they must provide sufficient, accurate and clear information to the media, public and other relevant groups (e.g., NGOs). Key requirements include systematic and coordinated research efforts to enable evidence-based decision making and to develop efficient policy measures on all scales (national, regional and global). To achieve this, collaboration between key actors is essential and should include researchers from multiple disciplines, policymakers, authorities, civil and industry organizations, and the public. This further requires clear and informative communication processes, and open and continuous dialogues between all actors. Cross-discipline dialogues between researchers should focus on scientific quality and harmonization, defining and accurately communicating the state of knowledge, and prioritization of topics that are critical for both research and policy, with the common goal to establish and update action plans for holistic benefit. In Norway, cross-sectoral collaboration has been fundamental in supporting the national strategy to address plastic pollution. Researchers, stakeholders and the environmental authorities have come together to exchange knowledge, identify knowledge gaps, and set targeted and feasible measures to tackle one of the most challenging aspects of plastic pollution: microplastic. In this article, we present a Norwegian perspective on the state of knowledge on microplastic research efforts. Norway's involvement in international efforts to combat plastic pollution aims at serving as an example of how key actors can collaborate synergistically to share knowledge, address shortcomings, and outline ways forward to address environmental challenges.