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The 2014 Nobel Prize in Physiology or Medicine, awarded to John O'Keefe, May-Britt Moser, and Edvard I. Moser, recognizes the first deep-brain insights into a cognitive function. Their insights established a new view for how the brain represents spatial location.
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Hipocampo/fisiología , Neurociencias/historia , Premio Nobel , Fisiología/historia , Animales , Canadá , Inglaterra , Historia del Siglo XX , Humanos , Noruega , Navegación EspacialRESUMEN
Recent discoveries of rapid changes in the atmospheric 14C concentration linked to solar particle events have spurred the construction of new radiocarbon annual calibration datasets1-13. With these datasets, radiocarbon dating becomes relevant for urban sites, which require dates at higher resolution than previous calibration datasets could offer. Here we use a single-year radiocarbon calibration curve to anchor the archaeological stratigraphy of a Viking Age trade centre in time. We present absolutely dated evidence for artefact finds charting the expansion of long-distance trade from as far away as Arctic Norway and the Middle East, which we linked to the beginning of the Viking Age at AD 790 ± 10. The methods developed here enable human interactions and cultural, climatic and environmental changes to be compared in archaeological stratigraphies worldwide.
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Arqueología , Datación Radiométrica , Calibración , Humanos , Medio Oriente , NoruegaRESUMEN
Major initiatives attempt to prevent dementia by targeting modifiable risk factors. Low education is frequently pointed to, due to its relationship with dementia. Impact of education is difficult to assess, however, because of associations with multiple other factors, requiring large population-representative samples to tease the relationships apart. We studied 207,814 Norwegian men born between 1950 and 1959 who underwent compulsory cognitive testing during military conscription as young adults, to systematically test associations of education, cognition, and other important factors. Participants were grouped into five education levels and seven cognitive levels. A total of 1,521 were diagnosed with dementia between ages 60 and 69 y. While having compulsory education only was associated with increased risk (Hazard ratio [HR] = 1.37, CI: 1.17 to 1.60), this association was markedly attenuated when controlling for cognitive test scores (HR = 1.08, CI: 0.91 to 1.28). In contrast, low cognitive score was associated with double risk of later diagnosis, even when controlling for education (HR = 2.00, CI: 1.65 to 2.42). This relationship survived controlling for early-life socioeconomic status and replicated within pairs of brothers. This suggests that genetic and environmental factors shared within families, e.g., common genetics, parental education, socioeconomic status, or other shared experiences, cannot account for the association. Rather, independent, nonfamilial factors are more important. In contrast, within-family factors accounted for the relationship between low education and diagnosis risk. In conclusion, implementing measures to increase cognitive function in childhood and adolescence appears to be a more promising strategy for reducing dementia burden.
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Cognición , Demencia , Escolaridad , Humanos , Demencia/epidemiología , Demencia/prevención & control , Masculino , Cognición/fisiología , Factores de Riesgo , Persona de Mediana Edad , Anciano , Noruega/epidemiología , AdolescenteRESUMEN
Chronic wasting disease (CWD) is a prion disease affecting deer, elk and moose in North America and reindeer, moose and red deer in Northern Europe. Pathogenesis is driven by the accumulation of PrPSc, a pathological form of the host's cellular prion protein (PrPC), in the brain. CWD is contagious among North American cervids and Norwegian reindeer, with prions commonly found in lymphatic tissue. In Nordic moose and red deer CWD appears exclusively in older animals, and prions are confined to the CNS and undetectable in lymphatic tissues, indicating a sporadic origin. We aimed to determine transmissibility, neuroinvasion and lymphotropism of Nordic CWD isolates using gene-targeted mice expressing either wild-type (138SS/226QQ) or S138N (138NN/226QQ) deer PrP. When challenged with North American CWD strains, mice expressing S138N PrP did not develop clinical disease but harbored prion seeding activity in brain and spleen. Here, we infected these models intracerebrally or intraperitoneally with Norwegian moose, red deer and reindeer CWD isolates. The moose isolate was the first CWD type to cause full-blown disease in the 138NN/226QQ model in the first passage, with 100% attack rate and shortened survival times upon second passage. Furthermore, we detected prion seeding activity or PrPSc in brains and spinal cords, but not spleens, of 138NN/226QQ mice inoculated intraperitoneally with the moose isolate, providing evidence of prion neuroinvasion. We also demonstrate, for the first time, that transmissibility of the red deer CWD isolate was restricted to transgenic mice overexpressing elk PrPC (138SS/226EE), identical to the PrP primary structure of the inoculum. Our findings highlight that susceptibility to clinical disease is determined by the conformational compatibility between prion inoculum and host PrP primary structure. Our study indicates that neuroinvasion of Norwegian moose prions can occur without, or only very limited, replication in the spleen, an unprecedented finding for CWD.
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Ciervos , Enfermedad Debilitante Crónica , Animales , Enfermedad Debilitante Crónica/transmisión , Enfermedad Debilitante Crónica/metabolismo , Ratones , Encéfalo/metabolismo , Encéfalo/patología , Proteínas Priónicas/metabolismo , Proteínas Priónicas/genética , Ratones Transgénicos , Noruega , Marcación de Gen , Priones/metabolismo , Priones/genética , Priones/patogenicidadRESUMEN
ABSTRACT: MicroRNA-145 (miR-145) has been reported to downregulate the expression of tissue factor and factor XI in vitro and decrease venous thrombus formation in animal models. However, the association between miR-145 and risk of future venous thromboembolism (VTE) in the general population remains unknown. We investigated the association between plasma levels of miR-145 and risk of future VTE in a case-cohort study. Incident VTE cases (n = 510) and a subcohort (n = 1890) were derived from the third survey of the Trøndelag Health Study (HUNT3), a population-based cohort. The expression levels of miR-145 were measured in plasma samples obtained at baseline. The study population was divided into quartiles based on miR-145 levels in participants in the subcohort, and weighted Cox regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Plasma levels of miR-145 were inversely associated with VTE risk. Participants with miR-145 levels in the highest quartile had a 49% lower risk of VTE (HR, 0.51; 95% CI, 0.38-0.68) than those with miR-145 in the lowest quartile in age- and sex-adjusted analysis, and the inverse association was most pronounced for unprovoked VTE (HR, 0.39; 95% CI, 0.25-0.61). Risk estimates remained virtually the same after further adjustment for body mass index, and cancer and arterial cardiovascular disease at baseline. In conclusion, elevated expression levels of miR-145 in plasma were associated with decreased risk of future incident VTE. The protective role of miR-145 against VTE is consistent with previous experimental data and suggests that miR-145 has the potential to be a target for VTE prevention.
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MicroARNs , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/sangre , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/genética , Masculino , MicroARNs/sangre , Femenino , Persona de Mediana Edad , Anciano , Incidencia , Factores de Riesgo , Adulto , Estudios de Cohortes , Noruega/epidemiología , Estudios de Casos y ControlesRESUMEN
Although life trajectories are frequently theorized to explain people's attitudes toward different social groups, few studies have been able to directly assess their importance with suitable data. Addressing this gap and focusing on the development of general and domain-specific self-esteem, we report results from a population-based sample of Norwegians (N = 2,215) followed over 28 years and five time points from adolescence to midlife. Growth curve models demonstrated that irrespective of self-esteem domain, low levels of self-esteem in adolescence as well as a depressed self-esteem development over the next three decades were related to more overall opposition to social equality as well as more opposition to gender equality and immigration in midlife. The results held when controlling for participants' baseline political orientations and other key covariates in adolescence. Our findings indicate that low self-esteem and a lack of positive self-esteem development can be detrimental to harmonious intergroup relations in ever-diversifying societies. We discuss how future psychological interventions aimed at enhancing self-esteem may promote support for a more inclusive society.
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Autoimagen , Adolescente , Humanos , Noruega , Estudios LongitudinalesRESUMEN
BACKGROUND: Formerly incarcerated people have exceptionally poor health profiles and are at increased risk of preventable mortality when compared with their general population peers. However, not enough is known about the epidemiology of mortality in this population-specifically the rates, causes, and timing of death in specific subgroups and regions-to inform the development of targeted, evidence-based responses. We aimed to document the incidence, timing, causes, and risk factors for mortality after release from incarceration. METHODS: We analysed linked administrative data from the multi-national Mortality After Release from Incarceration Consortium (MARIC) study. We examined mortality outcomes for 1 471 526 people released from incarceration in eight countries (Australia, Brazil, Canada, New Zealand, Norway, Scotland, Sweden, and the USA) from 1980 to 2018, across 10 534 441 person-years of follow-up (range 0-24 years per person). We combined data from 18 cohort studies using two-step individual participant data meta-analyses to estimate pooled all-cause and cause-specific crude mortality rates (CMRs) per 100 000 person-years, for specific time periods (first, daily from days 1-14; second, weekly from weeks 3-12; third, weeks 13-52 combined; fourth, weeks 53 and over combined; and fifth, total follow-up) after release, overall and stratified by age, sex, and region. FINDINGS: 75 427 deaths were recorded. The all-cause CMR during the first week following release (1612 [95% CI 1048-2287]) was higher than during all other time periods (incidence rate ratio [IRR] compared with week 2: 1·5 [95% CI 1·2-1·8], I2=26·0%, weeks 3-4: 2·0 [1·5-2·6], I2=53·0%, and weeks 9-12: 2·2 [1·6-3·0], I2=70·5%). The highest cause-specific mortality rates during the first week were due to alcohol and other drug poisoning (CMR 657 [95% CI 332-1076]), suicide (135 [36-277]), and cardiovascular disease (71 [16-153]). We observed considerable variation in cause-specific CMRs over time since release and across regions. Pooled all-cause CMRs were similar between males (731 [95% CI 630-839]) and females (660 [560-767]) and were higher in older age groups. INTERPRETATION: The markedly elevated rate of death in the first week post-release underscores an urgent need for investment in evidence-based, coordinated transitional healthcare, including treatment for mental illness and substance use disorders to prevent post-release deaths due to suicide and overdose. Temporal variations in rates and causes of death highlight the need for routine monitoring of post-release mortality. FUNDING: Australia's National Health and Medical Research Council.
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Causas de Muerte , Prisioneros , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Australia/epidemiología , Brasil/epidemiología , Canadá/epidemiología , Países Desarrollados/estadística & datos numéricos , Encarcelamiento , Incidencia , Nueva Zelanda/epidemiología , Noruega/epidemiología , Prisioneros/estadística & datos numéricos , Factores de Riesgo , Escocia/epidemiología , Suecia/epidemiologíaRESUMEN
The aetiology of conduct problems involves a combination of genetic and environmental factors, many of which are inherently linked to parental characteristics given parents' central role in children's lives across development. It is important to disentangle to what extent links between parental heritable characteristics and children's behaviour are due to transmission of genetic risk or due to parental indirect genetic influences via the environment (i.e., genetic nurture). We used 31,290 genotyped mother-father-child trios from the Norwegian Mother, Father and Child Cohort Study (MoBa), testing genetic transmission and genetic nurture effects on conduct problems using 13 polygenic scores (PGS) spanning psychiatric conditions, substance use, education-related factors, and other risk factors. Maternal or self-reports of conduct problems at ages 8 and 14 years were available for up to 15,477 children. We found significant genetic transmission effects on conduct problems for 12 out of 13 PGS at age 8 years (strongest association: PGS for smoking, ß = 0.07, 95% confidence interval = [0.05, 0.08]) and for 4 out of 13 PGS at age 14 years (strongest association: PGS for externalising problems, ß = 0.08, 95% confidence interval = [0.05, 0.11]). Conversely, we did not find genetic nurture effects for conduct problems using our selection of PGS. Our findings provide evidence for genetic transmission in the association between parental characteristics and child conduct problems. Our results may also indicate that genetic nurture via traits indexed by our polygenic scores is of limited aetiological importance for conduct problems-though effects of small magnitude or effects via parental traits not captured by the included PGS remain a possibility.
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Trastorno de la Conducta , Herencia Multifactorial , Humanos , Femenino , Niño , Noruega , Masculino , Adolescente , Factores de Riesgo , Herencia Multifactorial/genética , Estudios de Cohortes , Trastorno de la Conducta/genética , Trastorno de la Conducta/epidemiología , Adulto , Madres , Padre , Problema de Conducta , Predisposición Genética a la Enfermedad/genética , GenotipoRESUMEN
Epigenetic age acceleration (EAA), defined as the difference between chronological age and epigenetically predicted age, was calculated from multiple gestational epigenetic clocks (Bohlin, EPIC overlap, and Knight) using DNA methylation levels from cord blood in three large population-based birth cohorts: the Generation R Study (The Netherlands), the Avon Longitudinal Study of Parents and Children (United Kingdom), and the Norwegian Mother, Father and Child Cohort Study (Norway). We hypothesized that a lower EAA associates prospectively with increased ADHD symptoms. We tested our hypotheses in these three cohorts and meta-analyzed the results (n = 3383). We replicated previous research on the association between gestational age (GA) and ADHD. Both clinically measured gestational age as well as epigenetic age measures at birth were negatively associated with ADHD symptoms at ages 5-7 years (clinical GA: ß = -0.04, p < 0.001, Bohlin: ß = -0.05, p = 0.01; EPIC overlap: ß = -0.05, p = 0.01; Knight: ß = -0.01, p = 0.26). Raw EAA (difference between clinical and epigenetically estimated gestational age) was positively associated with ADHD in our main model, whereas residual EAA (raw EAA corrected for clinical gestational age) was not associated with ADHD symptoms across cohorts. Overall, findings support a link between lower gestational age (either measured clinically or using epigenetic-derived estimates) and ADHD symptoms. Epigenetic age acceleration does not, however, add unique information about ADHD risk independent of clinically estimated gestational age at birth.
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Trastorno por Déficit de Atención con Hiperactividad , Metilación de ADN , Epigénesis Genética , Edad Gestacional , Humanos , Trastorno por Déficit de Atención con Hiperactividad/genética , Femenino , Niño , Epigénesis Genética/genética , Masculino , Estudios Prospectivos , Metilación de ADN/genética , Preescolar , Reino Unido/epidemiología , Estudios Longitudinales , Países Bajos/epidemiología , Noruega , Estudios de Cohortes , Embarazo , Sangre Fetal/metabolismoRESUMEN
Vaccination was a key intervention in controlling the COVID-19 pandemic globally. In early 2021, Norway faced significant regional variations in COVID-19 incidence and prevalence, with large differences in population density, necessitating efficient vaccine allocation to reduce infections and severe outcomes. This study explored alternative vaccination strategies to minimize health outcomes (infections, hospitalizations, ICU admissions, deaths) by varying regions prioritized, extra doses prioritized, and implementation start time. Using two models (individual-based and meta-population), we simulated COVID-19 transmission during the primary vaccination period in Norway, covering the first 7 months of 2021. We investigated alternative strategies to allocate more vaccine doses to regions with a higher force of infection. We also examined the robustness of our results and highlighted potential structural differences between the two models. Our findings suggest that early vaccine prioritization could reduce COVID-19 related health outcomes by 8% to 20% compared to a baseline strategy without geographic prioritization. For minimizing infections, hospitalizations, or ICU admissions, the best strategy was to initially allocate all available vaccine doses to fewer high-risk municipalities, comprising approximately one-fourth of the population. For minimizing deaths, a moderate level of geographic prioritization, with approximately one-third of the population receiving doubled doses, gave the best outcomes by balancing the trade-off between vaccinating younger people in high-risk areas and older people in low-risk areas. The actual strategy implemented in Norway was a two-step moderate level aimed at maintaining the balance and ensuring ethical considerations and public trust. However, it did not offer significant advantages over the baseline strategy without geographic prioritization. Earlier implementation of geographic prioritization could have more effectively addressed the main wave of infections, substantially reducing the national burden of the pandemic.
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COVID-19 , Vacunas , Humanos , Anciano , Pandemias/prevención & control , COVID-19/epidemiología , COVID-19/prevención & control , Vacunación , Noruega/epidemiologíaAsunto(s)
Océanos y Mares , Desarrollo Sostenible , Noruega , Desarrollo Sostenible/economía , Desarrollo Sostenible/legislación & jurisprudencia , Desarrollo Sostenible/tendencias , Industria del Petróleo y Gas/legislación & jurisprudencia , Industria del Petróleo y Gas/tendencias , Minería/legislación & jurisprudencia , Minería/tendenciasRESUMEN
International initiatives for reducing carbon emissions from deforestation and forest degradation (REDD+) could make critical, cost-effective contributions to tropical countries' nationally determined contributions (NDCs). Norway, a key donor of such initiatives, had a REDD+ partnership with Indonesia, offering results-based payments in exchange for emissions reductions calculated against a historical baseline. Central to this partnership was an area-based moratorium on new oil palm, timber, and logging concessions in primary and peatland forests. We evaluate the effectiveness of the moratorium between 2011 and 2018 by applying a matched triple difference strategy to a unique panel dataset. Treated dryland forest inside moratorium areas retained, at most, an average of 0.65% higher forest cover compared to untreated dryland forest outside the moratorium. By contrast, carbon-rich peatland forest was unaffected by the moratorium. Cumulative avoided dryland deforestation from 2011 until 2018 translates into 67.8 million to 86.9 million tons of emissions reductions, implying an effective carbon price below Norway's US$5 per ton price. Based on Norway's price, our estimated cumulative emissions reductions are equivalent to a payment of US$339 million to US$434.5 million. Annually, our estimates suggest a 3 to 4% contribution to Indonesia's NDC commitment of a 29% emissions reduction by 2030. Despite the Indonesia-Norway partnership ending in 2021, reducing emissions from deforestation remains critical for meeting this commitment. Future area-based REDD+ initiatives could build on the moratorium's outcomes by reforming its incentives and institutional arrangements, particularly in peatland forest areas.
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Carbono/economía , Conservación de los Recursos Naturales/economía , Análisis Costo-Beneficio/economía , Cambio Climático/economía , Bosques , Indonesia , Noruega , Aceite de Palma/economía , ParisRESUMEN
BACKGROUND: The global incidence target for the elimination of hepatitis C among people who inject drugs (PWID) is <2/100. In Norway, the hepatitis C epidemic is concentrated in PWID. Immigrants are the second most important risk group for chronic infection. We modelled the incidence of hepatitis C among active PWID, and the prevalence of chronic infection among active PWID, ex-PWID, and immigrants in Norway to 2022. METHODS: We built a stochastic compartmental model, which was informed using data from national data sources, literature, and expert opinion. We report median values with 95% credible intervals (CrI). RESULTS: The model estimated 30 (95% Crl, 13-52) new infections among active PWID in 2022, or 0.37/100 (95% Crl, 0.17-0.65), down from a peak of 726 (95% Crl, 506-1067) in 2000. Across all groups, the model estimated 3202 (95% Crl, 1273-6601) chronically infected persons in 2022. Results were robust in sensitivity analyses. CONCLUSIONS: Norway provides an example of the feasibility of hepatitis C elimination in a setting with a concentrated epidemic, high coverage of harm reduction services, and no treatment restrictions. Continued momentum is needed to further reduce the transmission and burden of hepatitis C in Norway.
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Emigrantes e Inmigrantes , Hepatitis C , Abuso de Sustancias por Vía Intravenosa , Humanos , Noruega/epidemiología , Abuso de Sustancias por Vía Intravenosa/epidemiología , Hepatitis C/epidemiología , Hepatitis C/prevención & control , Emigrantes e Inmigrantes/estadística & datos numéricos , Prevalencia , Incidencia , Salud Pública , Masculino , Adulto , Femenino , Erradicación de la Enfermedad , Persona de Mediana EdadRESUMEN
AIMS/HYPOTHESIS: Children and adults born preterm have an increased risk of type 1 diabetes. However, there is limited information on risk patterns across the full range of gestational ages, especially after extremely preterm birth (23-27 weeks of gestation). We investigated the risk of type 1 diabetes in childhood and young adulthood across the full range of length of gestation at birth. METHODS: Data were obtained from national registers in Finland, Norway and Sweden. In each country, information on study participants and gestational age was collected from the Medical Birth Registers, information on type 1 diabetes diagnoses was collected from the National Patient Registers, and information on education, emigration and death was collected from the respective national register sources. Individual-level data were linked using unique personal identity codes. The study population included all individuals born alive between 1987 and 2016 to mothers whose country of birth was the respective Nordic country. Individuals were followed until diagnosis of type 1 diabetes, death, emigration or end of follow-up (31 December 2016 in Finland, 31 December 2017 in Norway and Sweden). Gestational age was categorised as extremely preterm (23-27 completed weeks), very preterm (28-31 weeks), moderately preterm (32-33 weeks), late preterm (34-36 weeks), early term (37-38 weeks), full term (39-41 weeks; reference) and post term (42-45 weeks). HRs and 95% CIs from country-specific covariate-adjusted Cox regression models were combined in a meta-analysis using a common-effect inverse-variance model. RESULTS: Among 5,501,276 individuals, 0.2% were born extremely preterm, 0.5% very preterm, 0.7% moderately preterm, 4.2% late preterm, 17.7% early term, 69.9% full term, and 6.7% post term. A type 1 diabetes diagnosis was recorded in 12,326 (0.8%), 6364 (0.5%) and 16,856 (0.7%) individuals at a median age of 8.2, 13.0 and 10.5 years in Finland, Norway and Sweden, respectively. Individuals born late preterm or early term had an increased risk of type 1 diabetes compared with their full-term-born peers (pooled, multiple confounder-adjusted HR 1.12, 95% CI 1.07, 1.18; and 1.15, 95% CI 1.11, 1.18, respectively). However, those born extremely preterm or very preterm had a decreased risk of type 1 diabetes (adjusted HR 0.63, 95% CI 0.45, 0.88; and 0.78, 95% CI 0.67, 0.92, respectively). These associations were similar across all three countries. CONCLUSIONS/INTERPRETATION: Individuals born late preterm and early term have an increased risk of type 1 diabetes while individuals born extremely preterm or very preterm have a decreased risk of type 1 diabetes compared with those born full term.
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Diabetes Mellitus Tipo 1 , Edad Gestacional , Sistema de Registros , Humanos , Diabetes Mellitus Tipo 1/epidemiología , Finlandia/epidemiología , Noruega/epidemiología , Suecia/epidemiología , Femenino , Masculino , Recién Nacido , Niño , Adolescente , Adulto Joven , Nacimiento Prematuro/epidemiología , Factores de Riesgo , Adulto , EmbarazoRESUMEN
AIMS/HYPOTHESIS: The aim of this study was to investigate whether higher dietary intake of marine n-3 fatty acids during pregnancy is associated with a lower risk of type 1 diabetes in children. METHODS: The Danish National Birth Cohort (DNBC) and the Norwegian Mother, Father and Child Cohort Study (MoBa) together include 153,843 mother-child pairs with prospectively collected data on eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake during pregnancy from validated food frequency questionnaires. Type 1 diabetes diagnosis in children (n=634) was ascertained from national diabetes registries. RESULTS: There was no association between the sum of EPA and DHA intake during pregnancy and risk of type 1 diabetes in offspring (pooled HR per g/day of intake: 1.00, 95% CI 0.88, 1.14), with consistent results for both the MoBa and the DNBC. Robustness analyses gave very similar results. CONCLUSIONS/INTERPRETATION: Initiation of a trial of EPA and DHA during pregnancy to prevent type 1 diabetes in offspring should not be prioritised.
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Diabetes Mellitus Tipo 1 , Ácidos Grasos Omega-3 , Humanos , Embarazo , Diabetes Mellitus Tipo 1/epidemiología , Femenino , Ácidos Grasos Omega-3/administración & dosificación , Ácidos Docosahexaenoicos/administración & dosificación , Adulto , Dinamarca/epidemiología , Ácido Eicosapentaenoico/administración & dosificación , Noruega/epidemiología , Masculino , Estudios de Cohortes , Efectos Tardíos de la Exposición Prenatal/epidemiología , Factores de Riesgo , NiñoRESUMEN
As Norway considers revising triage approaches following their first adolescent cohort with human papillomavirus (HPV) vaccination entering the cervical cancer screening program, we analyzed the health impact and cost-effectiveness of alternative primary HPV triage approaches for women initiating cervical cancer screening in 2023. We used a multimodeling approach that captured HPV transmission and cervical carcinogenesis to evaluate the health benefits, harms and cost-effectiveness of alternative extended genotyping and age-based triage strategies under five-yearly primary HPV testing (including the status-quo screening strategy in Norway) for women born in 1998 (ie, age 25 in 2023). We examined 35 strategies that varied alternative groupings of high-risk HPV genotypes ("high-risk" genotypes; "medium-risk" genotypes or "intermediate-risk" genotypes), number and types of HPV included in each group, management of HPV-positive women to direct colposcopy or active surveillance, wait time for re-testing and age at which the HPV triage algorithm switched from less to more intensive strategies. Given the range of benchmarks for severity-specific cost-effectiveness thresholds in Norway, we found that the preferred strategy for vaccinated women aged 25 years in 2023 involved an age-based switch from a less to more intensive follow-up algorithm at age 30 or 35 years with HPV-16/18 genotypes in the "high-risk" group. The two potentially cost-effective strategies could reduce the number of colposcopies compared to current guidelines and simultaneously improve health benefits. Using age to guide primary HPV triage, paired with selective HPV genotype and follow-up time for re-testing, could improve both the cervical cancer program effectiveness and efficiency.
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Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Adolescente , Embarazo , Femenino , Humanos , Adulto , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/prevención & control , Virus del Papiloma Humano , Análisis Costo-Beneficio , Papillomavirus Humano 16/genética , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/prevención & control , Infecciones por Papillomavirus/epidemiología , Triaje , Detección Precoz del Cáncer , Papillomavirus Humano 18/genética , Colposcopía , NoruegaRESUMEN
Endometrial cancer (EC) is one of the most common female cancers and there is currently no routine screening strategy for early detection. An altered abundance of circulating microRNAs (miRNAs) and other RNA classes have the potential as early cancer biomarkers. We analyzed circulating RNA levels using small RNA sequencing, targeting RNAs in the size range of 17-47 nucleotides, in EC patients with samples collected prior to diagnosis compared to cancer-free controls. The analysis included 316 cases with samples collected 1-11 years prior to EC diagnosis, and 316 matched controls, both from the Janus Serum Bank cohort in Norway. We identified differentially abundant (DA) miRNAs, isomiRs, and small nuclear RNAs between EC cases and controls. The top EC DA miRNAs were miR-155-5p, miR-200b-3p, miR-589-5p, miR-151a-5p, miR-543, miR-485-5p, miR-625-p, and miR-671-3p. miR-200b-3p was previously reported to be among one of the top miRNAs with higher abundance in EC cases. We observed 47, 41, and 32 DA miRNAs for EC interacting with BMI, smoking status, and physical activity, respectively, including two miRNAs (miR-223-3p and miR-29b-3p) interacting with all three factors. The circulating RNAs are altered and show temporal dynamics prior to EC diagnosis. Notably, DA miRNAs for EC had the lowest q-value 4.39-6.66 years before diagnosis. Enrichment analysis of miRNAs showed that signaling pathways Fc epsilon RI, prolactin, toll-like receptor, and VEGF had the strongest associations.
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Biomarcadores de Tumor , Neoplasias Endometriales , Humanos , Femenino , Neoplasias Endometriales/sangre , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/genética , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Persona de Mediana Edad , Anciano , MicroARN Circulante/sangre , Estudios de Casos y Controles , MicroARNs/sangre , MicroARNs/genética , Regulación Neoplásica de la Expresión Génica , Noruega/epidemiología , AdultoRESUMEN
With the objective to investigate associations between sociodemographic characteristics and participation in interventions designed to increase participation in cervical cancer screening among under-screened women, we randomized a random sample of 6000 women in Norway aged 35-69 years who had not attended cervical screening for ≥10 years to receive either (i) a reminder to attend regular screening (control), (ii) an offer to order a self-sampling kit (opt-in), or (iii) a self-sampling kit unsolicited (send-to-all). We analyzed how sociodemographic characteristics were associated with screening participation within and between screening arms. In the send-to-all arm, increased screening participation ranged from 17.1% (95% confidence interval [95% CI] = 10.3% to 23.8%) to 30.0% (95% CI = 21.5% to 38.6%) between sociodemographic groups. In the opt-in arm, we observed smaller, and at times, non-significant increases within the range 0.7% (95% CI = -5.8% to 7.3%) to 19.1% (95% CI = 11.6% to 26.7%). In send-to-all versus control comparisons, there was greater increase in participation for women in the workforce versus not (6.1%, 95% CI = 1.6% to 10.6%), with higher versus lower income (7.6%, 95% CI = 2.2% to 13.1%), and with university versus primary education (8.5%, 95% CI = 2.4% to 14.6%). In opt-in versus control comparisons, there was greater increase in participation for women in the workforce versus not (4.6%, 95% CI = 0.7% to 8.5%), with higher versus lower income (6.3%, 95% CI = 1.5% to 11.1%), but lower increase for Eastern European versus Norwegian background (-12.7%, 95% CI = -19.7% to -5.7%). Self-sampling increased cervical screening participation across all sociodemographic levels, but inequalities in participation should be considered when introducing self-sampling, especially with the goal to reach long-term non-attending women.