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Fertility in patients with advanced-stage classic Hodgkin lymphoma treated with BrECADD versus eBEACOPP : a secondary analysis of the multicentre, randomised, parallel, open-label, phase 3 HD21 trial
No full textBackground BrECADD (brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone) has shown higher efficacy and better acute tolerability than eBEACOPP (escalated doses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) in newly diagnosed, advanced-stage classic Hodgkin lymphoma. In this secondary analysis of the HD21 trial, we aimed to compare gonadal function recovery and fertility outcomes between these two regimens. Methods In the multicentre, parallel, open-label, phase 3 HD21 trial, conducted across 233 trial sites in nine countries, patients aged 18-60 years with newly diagnosed, advanced-stage classic Hodgkin lymphoma and an Eastern Cooperative Oncology Group performance status of 0-2 were randomly assigned (1:1) to receive 4-6 cycles of eBEACOPP or BrECADD, guided by interim response. Patients and investigators were not masked to treatment assignment. Primary outcomes were progression-free survival and treatment-related morbidity (reported elsewhere). Here we report an unplanned analysis of fertility outcomes. Fertility outcomes included gonadal function recovery (via follicle-stimulating hormone [FSH] concentrations), concentrations of anti-M & uuml;llerian hormone (AMH; women only) and inhibin B (men only), frequencies of pregnancies, and incidence of parenthood. Gonadal function recovery, AMH, and inhibin B were assessed in the patients of childbearing potential (POCBP) cohort, which included women younger than 40 years and men younger than 50 years without baseline gonadal dysfunction. Pregnancy and parenthood analyses also included patients with baseline gonadal dysfunction. The HD21 trial was registered at ClinicalTrials.gov (NCT02661503) and is ongoing but closed to enrolment. Findings Between July 22, 2016, and Aug 27, 2020, 1183 POCBP were enrolled (592 in the eBEACOPP group, 591 in the BrECADD group; 692 men, 491 women). FSH measurements were available for 767 patients (420 men and 347 women). Median follow-up was 49<middle dot>6 months (IQR 39<middle dot>7-58<middle dot>4). BrECADD was associated with significantly higher 4-year gonadal function recovery rates compared with eBEACOPP (95<middle dot>3% [95% CI 92<middle dot>0-98<middle dot>8] in the BrECADD group vs 73<middle dot>3% [66<middle dot>9-80<middle dot>4] in the eBEACOPP group, HR 1<middle dot>69 [95% CI 1<middle dot>34-2<middle dot>14] in women; 85<middle dot>6% [80<middle dot>8-90<middle dot>8] vs 39<middle dot>7% [33<middle dot>6-46<middle dot>9], HR 3<middle dot>28 [2<middle dot>51-4<middle dot>30] in men). AMH and inhibin B concentrations were generally higher in the BrECADD group compared with the eBEACOPP group. A total of 92 pregnancies were reported among female patients, and 36 among partners of male patients. These led to 108 reported childbirths in 99 patients (59 in the BrECADD group and 40 in the eBEACOPP group). After therapy, 5-year incidence of parenthood was significantly higher in men (9<middle dot>3% [95% CI 6<middle dot>0-14<middle dot>5] vs 3<middle dot>3% [1<middle dot>7-6<middle dot>5], p=0<middle dot>014), but not significantly higher in women (19<middle dot>3% [13<middle dot>7-27<middle dot>3] vs 17<middle dot>1% [11<middle dot>9-24<middle dot>6], p=0<middle dot>53) with BrECADD versus eBEACOPP. Interpretation Compared with eBEACOPP, BrECADD led to significantly better gonadal function recovery, as well as higher parenthood rates (significantly so in men). These findings support BrECADD as preferred first-line therapy, especially for patients wishing to preserve fertility. Copyright (c) 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
Association of biological, socioeconomic, and environmental factors with child development at two years of age in Bangladesh, Pakistan, and Tanzania : results from the AMANHI-ACT study
No full textBackground The first 1,000 days of life, spanning pregnancy to two years, are critical for development. We investigated the association of maternal, socioeconomic, environmental, nutritional, and childhood characteristics with cognitive, motor, and language development at two years of age. Methods The AMANHI-ACT study enrolled pregnant women between 8 and 19 weeks of gestation from Bangladesh, Pakistan, and Tanzania. Data was collected on sociodemographic factors, maternal BMI and co-morbidities during pregnancy, and weight and gestational age at birth. Child characteristics included vaccination history, infections, and physical growth at predefined intervals up to two years. Child development at two years was assessed using the Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III). The home environment was assessed using the Home Observation for Measurement of the Environment Infant-Toddler (HOME-IT) tool. We performed linear regression and reported site-adjusted regression coefficients with 95% confidence intervals. Results We assessed 3,062 children at two years of age to identify factors associated with their cognitive, language, and motor development scores. Cognitive scores were significantly lower among children whose mothers had no formal education (Adjusted coefficient = -3.8; 95% CI: -5.8, -1.8) and those who had not received any vaccinations (Adjusted coefficient = -6.0; 95% CI: -9.3, -2.6). Language development was similarly affected: children with mothers who had no education (Adjusted coefficient = -4.7; 95% CI: -6.8, -2.5) or only primary-level education (Adjusted coefficient = -4.5; 95% CI: -6.5, -2.5) showed markedly lower scores. Language scores were also reduced in children whose fathers had no education (Adjusted coefficient = -2.4; 95% CI: -4.2, -0.5) or only primary education (Adjusted coefficient = -2.4; 95% CI: -4.1, -0.6). For motor development, children who were stunted (Adjusted coefficient = -2.2; 95% CI: -2.9, -1.4), wasted (Adjusted coefficient = -2.8; 95% CI: -4.3, -1.4), or unvaccinated (Adjusted coefficient = -4.7; 95% CI: -8.0, -1.4) at two years exhibited significantly lower scores. Conclusion Preterm births, vaccination history, parental education, and physical growth significantly affected the first 1000 days of child development, thus identifying areas for targeted intervention to optimize long-term health outcomes in LMICs
Real-world survival outcomes of neoadjuvant versus adjuvant chemotherapy in operable triple-negative breast cancer : a propensity score matched registry-based study
No full textBackground and purpose: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype where the prognostic implications of primary systemic therapy followed by surgery, compared to up-front surgery and subsequent adjuvant chemotherapy (ACT), are yet to be outlined. This retrospective registry-based study aimed to compare survival outcomes between patients treated with neoadjuvant chemotherapy (NACT) versus ACT for operable TNBC in a real-world setting. Patient/material and methods: We included all patients treated with chemotherapy for operable TNBC in Sweden between 2008 and 2019 using the Swedish national research database BCBaSe 3.0. To reduce confounding by indication, we implemented propensity score matching (PSM) and main study outcomes were defined as distant disease-free survival (DDFS), breast cancer-specific survival (BCSS) and overall survival (OS). Results: A total of 4,704 patients were included in the study, of which 1,183 received NACT. Following 1:1 PSM, 837 patients in each treatment setting were available for analyses. We found no statistically significant differences in terms of DDFS (adjusted hazard ratio [aHR] 1.18; 95% confidence interval [CI] 0.93-1.50), BCSS (aHR 1.10; 95% CI 0.83-1.45) or OS (aHR 1.07; 95% CI 0.82-1.39) between patients treated with NACT versus ACT. However, subgroup analysis of patients with clinically node-positive disease (cN+) demonstrated a significant DDFS benefit of NACT (aHR 0.65; 95% CI 0.47-0.90). Interpretation: Overall, we found comparable survival among patients with TNBC treated with NACT or ACT. Considering the anticipated survival improvements when response-guided post-neoadjuvant strategies are implemented in clinical practice, our findings may support the use of NACT in operable TNBC
HIV and tuberculosis co-infection in non-European migrants in Europe : a systematic review and meta-analysis
No full textBackground Even though HIV-TB co-infection is an emerging public health issue among migrants in European countries, the number of related articles has shown a decreasing trend. Methods To better estimate the extent of this problem, we analyzed 34 articles reporting both prevalence and odds ratio for HIV-TB co-infection in migrants in European countries. Heterogeneity analysis was conducted to assess potential bias, and a random-effects model was used to calculate the effect size. Results The overall prevalence of HIV-TB co-infection was 9% (95%CI: 7% − 11%) in foreign-born individuals, with higher rates observed in specific subgroups: 14% (95%CI: 5% − 33%) in those from Sub-Saharan Africa, which is higher than the overall average, and 4% (95%CI: 2% − 7%) in those from Latin America, which is lower than the overall average. Compared to the native-born European population, foreign-born individuals had a twofold increased risk of HIV-TB co-infection, with a threefold increased risk for those from Sub-Saharan Africa. Conclusions Our meta-analysis results highlight the disproportionate burden of HIV-TB co-infection among foreign-born people in Europe, particularly those from Sub-Saharan Africa
Inclusive or exclusive? : Candidate selection methods do not affect descriptive representation
No full textCandidate selection practices are often highlighted as a key factor in explaining the political underrepresentation of marginalised groups, such as women, ethnic minorities, or youth. Conventional wisdom holds that exclusive candidate selection methods, such as selection committees, tend to yield more descriptively representative outcomes than inclusive methods, such as primaries. However, these conclusions are often drawn from cross-sectional comparisons between parties with different selection methods. This article leverages an original conjoint experiment in Sweden to compare the demand for different candidate profiles, including women, youth, and immigrants, among party members (N = 6400) and selection committee members (N = 1300) under two modes of candidate selection: primaries and selection committees. The findings reveal strikingly similar preferences for underrepresented candidate profiles across both groups and selection modes. These results suggest that, within a favourable institutional framework, both inclusive and exclusive selection procedures can be equally effective in promoting descriptive representation
How exposure to wartime violence shapes conflict resolution preferences
No full textWartime violence profoundly shapes attitudes and political behavior, yet its impact on preferences for specific conflict resolution strategies remains underexplored. Using survey data (n = 1452) from Syrian refugees in a Turkish UNHCR camp, we analyze how the severity and type of violence experienced during the Syrian Civil War influence support for various conflict resolution options. Our findings support the “war-weariness” hypothesis: individuals exposed to severe, direct violence favor political solutions like ceasefires, negotiations, and elections, expected to address immediate safety needs. Our findings have significant implications for peacebuilders, highlighting the importance of considering diverse conflict experiences when designing effective peace initiatives
Global, regional, and national progress towards the 2030 global nutrition targets and forecasts to 2050 : a systematic analysis for the Global Burden of Disease Study 2021
No full textBackkground: The six global nutrition targets (GNTs) related to low birthweight, exclusive breastfeeding, child growth (ie, wasting, stunting, and overweight), and anaemia among females of reproductive age were chosen by the World Health Assembly in 2012 as key indicators of maternal and child health, but there has yet to be a comprehensive report on progress for the period 2012 to 2021. We aimed to evaluate levels, trends, and observed-to-expected progress in prevalence and attributable burden from 2012 to 2021, with prevalence projections to 2050, in 204 countries and territories. Methods: The prevalence and attributable burden of each target indicator were estimated by age group, sex, and year in 204 countries and territories from 2012 to 2021 in the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, the most comprehensive assessment of causes of death, disability, and risk factors to date. Country-specific relative performance to date was evaluated with a Bayesian meta-regression model that compares prevalence to expected values based on Socio-demographic Index (SDI), a composite indicator of societal development status. Target progress was forecasted from 2021 up to 2050 by modelling past trends with meta-regression using a combination of key quantities and then extrapolating future projections of those quantities. Findings: In 2021, a few countries had already met some of the GNTs: five for exclusive breastfeeding, four for stunting, 96 for child wasting, and three for child overweight, and none met the target for low birthweight or anaemia in females of reproductive age. Since 2012, the annualised rates of change (ARC) in the prevalence of child overweight increased in 201 countries and territories and ARC in the prevalence of anaemia in females of reproductive age decreased considerably in 26 countries. Between 2012 and 2021, SDI was strongly associated with indicator prevalence, apart from exclusive breastfeeding (|r-|=0·46-0·86). Many countries in sub-Saharan Africa had a decrease in the prevalence of multiple indicators that was more rapid than expected on the basis of SDI (the differences between observed and expected ARCs for child stunting and wasting were -0·5% and -1·3%, respectively). The ARC in the attributable burden of low birthweight, child stunting, and child wasting decreased faster than the ARC of the prevalence for each in most low-income and middle-income countries. In 2030, we project that 94 countries will meet one of the six targets, 21 countries will meet two targets, and 89 countries will not meet any targets. We project that seven countries will meet the target for exclusive breastfeeding, 28 for child stunting, and 101 for child wasting, and no countries will meet the targets for low birthweight, child overweight, and anaemia. In 2050, we project that seven additional countries will meet the target for exclusive breastfeeding, five for low birthweight, 96 for child stunting, nine for child wasting, and one for child overweight, and no countries are projected to meet the anaemia target. Interpretation: Based on current levels and past trends, few GNTs will be met by 2030. Major reductions in attributable burden for exclusive breastfeeding and anthropometric indicators should be recognised as huge scientific and policy successes, but the comparative lack of progress in reducing the prevalence of each, along with stagnant anaemia in women of reproductive age and widespread increases in child overweight, suggests a tenuous status quo. Continued investment in preventive and treatment efforts for acute childhood illness is crucial to prevent backsliding. Parallel development of effective treatments, along with commitment to multisectoral, long-term policies to address the determinants and causes of suboptimal nutrition, are sorely needed to gain ground
Outreach health-care services for people experiencing exclusion in high-income countries
No full textInclusion health aims to prevent and address health and social inequalities for people experiencing exclusion, such as people experiencing homelessness, people who have a history of contact with the criminal justice system, people who use drugs, sex workers, vulnerable migrants, victims of modern slavery and human trafficking, and Romany Gypsy, Roma, and Travellers communities. These populations have poor health outcomes and disproportionate health inequities, partly resulting from inadequate health-care access. Outreach services can improve health-care access, but there is little evidence of how outreach operates successfully. We conducted a realist review of multicomponent outreach health-care services to understand the circumstances under which outreach works for people experiencing exclusion and why. Key components of effective outreach include person-centred services and appointments, staff expertise, high-quality communication, and close partnership with people experiencing exclusion and relevant organisations. Service users are likely to develop trust and further engage through positive experiences and regular interaction with the same staff
The quest to discover supersymmetry at the ATLAS experiment
No full textThe search for supersymmetry with the ATLAS experiment at the CERN Large Hadron Collider intensified after the discovery of the Higgs boson in 2012. The search programme expanded in both breadth and depth, profiting from the increased integrated luminosity and higher centre-of-mass energy for the collision data collected between 2015 and 2018, and gaining new sensitivity to unexplored areas of supersymmetry parameter space through the use of novel experimental signatures and innovative analysis techniques. This report summarises the supersymmetry searches at ATLAS using up to 140 fb(-1) of pp collisions at root s = 13 TeV, including the limits set on the production of gluinos, squarks, and electroweakinos for scenarios with or without R-parity conservation, and including models where some of the supersymmetric particles are long-lived. (c) 2024 CERN for the benefit of the ATLAS Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).For complete list of authors see http://dx.doi.org/10.1016/j.physrep.2024.09.010</p
Orbital parameters of exoplanets with multiple host stars
No full textThis paper aimed to reproduce some of the findings from González-Payo et al. (2024). Due to the use of a smaller data set, the error margins in this paper were significantly larger. However, the overall trends still corresponded well with González-Payo et al. (2024). There did not seem to be a strong correlation between eccentricity and star-star separation on its own. But when the relation between eccentricity and the ratio between star-star separation and the semi-major axis was measured, one could see a significant relationship between the two.Målet med detta projekt var att reproducera resultat från González-Payo m. fl. (2024). På grund av att detta projekt använde sig av ett mindre dataset innebar det att felmarginalerna blev betydligt större. De övergripande trenderna stämde däremot fortfarande väl gentemot resultaten från González-Payo m. fl. (2024). Det fanns ej enstark korrelation mellan excentriciteten och planeternas halva storaxel. Men när relationen mellan excentriciteten och kvoten av den halva storaxeln och stjärnornas avstånd till varandra mättes så kunde man se en stark korrelation