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- Blach, S., et al.
(author)
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Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study
- 2022
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In: Lancet Gastroenterology & Hepatology. - : Elsevier BV. - 2468-1253. ; 7:5, s. 396-415
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Journal article (peer-reviewed)abstract
- Background Since the release of the first global hepatitis elimination targets in 2016, and until the COVID-19 pandemic started in early 2020, many countries and territories were making progress toward hepatitis C virus (HCV) elimination. This study aims to evaluate HCV burden in 2020, and forecast HCV burden by 2030 given current trends. Methods This analysis includes a literature review, Delphi process, and mathematical modelling to estimate HCV prevalence (viraemic infection, defined as HCV RNA-positive cases) and the cascade of care among people of all ages (age =0 years from birth) for the period between Jan 1, 2015, and Dec 31, 2030. Epidemiological data were collected from published sources and grey literature (including government reports and personal communications) and were validated among country and territory experts. A Markov model was used to forecast disease burden and cascade of care from 1950 to 2050 for countries and territories with data. Model outcomes were extracted from 2015 to 2030 to calculate population-weighted regional averages, which were used for countries or territories without data. Regional and global estimates of HCV prevalence, cascade of care, and disease burden were calculated based on 235 countries and territories. Findings Models were built for 110 countries or territories: 83 were approved by local experts and 27 were based on published data alone. Using data from these models, plus population-weighted regional averages for countries and territories without models (n=125), we estimated a global prevalence of viraemic HCV infection of 0.7% (95% UI 0.7-0.9), corresponding to 56.8 million (95% UI 55.2-67.8) infections, on Jan 1, 2020. This number represents a decrease of 6.8 million viraemic infections from a 2015 (beginning of year) prevalence estimate of 63.6 million (61.8-75.8) infections (0.9% [0.8-1.0] prevalence). By the end of 2020, an estimated 12.9 million (12.5-15.4) people were living with a diagnosed viraemic infection. In 2020, an estimated 641 000 (623 000-765 000) patients initiated treatment. Interpretation At the beginning of 2020, there were an estimated 56.8 million viraemic HCV infections globally. Although this number represents a decrease from 2015, our forecasts suggest we are not currently on track to achieve global elimination targets by 2030. As countries recover from COVID-19, these findings can help refocus efforts aimed at HCV elimination. Copyright (C) 2022 Elsevier Ltd. All rights reserved.
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- Razavi, H., et al.
(author)
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Hepatitis C virus prevalence and level of intervention required to achieve the WHO targets for elimination in the European Union by 2030: a modelling study
- 2017
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In: Lancet Gastroenterology & Hepatology. - : Elsevier BV. - 2468-1253. ; 2:5, s. 325-336
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Journal article (peer-reviewed)abstract
- Background Hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality worldwide. In the European Union (EU), treatment and cure of HCV with direct-acting antiviral therapies began in 2014. WHO targets are to achieve a 65% reduction in liver-related deaths, a 90% reduction of new viral hepatitis infections, and 90% of patients with viral hepatitis infections being diagnosed by 2030. This study assessed the prevalence of HCV in the EU and the level of intervention required to achieve WHO targets for HCV elimination. Methods We populated country Markov models for the 28 EU countries through a literature search of PubMed and Embase between Jan 1, 2000, and March 31, 2016, and a Delphi process to gain expert consensus and validate inputs. We aggregated country models to create a regional EU model. We used the EU model to forecast HCV disease progression (considering the effect of immigration) and developed a strategy to acehive WHO targets. We used weighted average sustained viral response rates and fibrosis restrictions to model the effect of current therapeutic guidelines. We used the EU model to forecast HCV disease progression (considering the effect of immigration) under current screening and therapeutic guidelines. Additionally, we back-calculated the total number of patients needing to be screened and treated to achieve WHO targets. Findings We estimated the number of viraemic HCV infections in 2015 to be 3 238 000 (95% uncertainty interval [UI] 2 106 000-3 795 000) of a total population of 509 868 000 in the EU, equating to a prevalence of viraemic HCV of 0.64% (95% UI 0.41-0.74). We estimated that 1 180 000 (95% UI 1 003 000-1 357 000) people were diagnosed with viraemia (36.4%), 150 000 (12 000-180 000) were treated (4.6% of the total infected population or 12.7% of the diagnosed population), 133 000 (106 000-160 000) were cured (4.1%), and 57 900 (43 900-67 300) were newly infected (1.8%) in 2015. Additionally, 30 400 (26 600-42 500) HCV-positive immigrants entered the EU. To achieve WHO targets, unrestricted treatment needs to increase from 150 000 patients in 2015 to 187 000 patients in 2025 and diagnosis needs to increase from 88 800 new cases annually in 2015 to 180 000 in 2025. Interpretation Given its advanced health-care infrastructure, the EU is uniquely poised to eliminate HCV; however, expansion of screening programmes is essential to increase treatment to achieve the WHO targets. A united effort, grounded in sound epidemiological evidence, will also be necessary.
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- Razavi, Homie A., et al.
(author)
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Hepatitis D double reflex testing of all hepatitis B carriers in low-HBV- and high-HBV/HDV-prevalence countries
- 2023
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In: JOURNAL OF HEPATOLOGY. - : Elsevier. - 0168-8278 .- 1600-0641. ; 79:2, s. 576-580
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Journal article (peer-reviewed)abstract
- Hepatitis D virus (HDV) infection occurs as a coinfection with hepatitis B and increases the risk of hepatocellular carcinoma, decompensated cirrhosis, and mortality compared to hepatitis B virus (HBV) monoinfection. Reliable estimates of the prevalence of HDV infection and disease burden are essential to formulate strategies to find coinfected individuals more effectively and efficiently. The global prevalence of HBV infections was estimated to be 262,240,000 in 2021. Only 1,994,000 of the HBV in-fections were newly diagnosed in 2021, with more than half of the new diagnoses made in China. Our initial estimates indicated a much lower prevalence of HDV antibody (anti-HDV) and HDV RNA positivity than previously reported in published studies. Ac-curate estimates of HDV prevalence are needed. The most effective method to generate estimates of the prevalence of anti-HDV and HDV RNA positivity and to find undiagnosed individuals at the national level is to implement double reflex testing. This re-quires anti-HDV testing of all hepatitis B surface antigen-positive individuals and HDV RNA testing of all anti-HDV-positive in-dividuals. This strategy is manageable for healthcare systems since the number of newly diagnosed HBV cases is low. At the global level, a comprehensive HDV screening strategy would require only 1,994,000 HDV antibody tests and less than 89,000 HDV PCR tests. Double reflex testing is the preferred strategy in countries with a low prevalence of HBV and those with a high prevalence of both HBV and HDV. For example, in the European Union and North America only 35,000 and 22,000 cases, respectively, will require anti-HDV testing annually.
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- Criado, M. G., et al.
(author)
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Plant traits poorly predict winner and loser shrub species in a warming tundra biome
- 2023
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In: Nature Communications. - 2041-1723. ; 14:1
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Journal article (peer-reviewed)abstract
- Climate change is leading to species redistributions. In the tundra biome, shrubs are generally expanding, but not all tundra shrub species will benefit from warming. Winner and loser species, and the characteristics that may determine success or failure, have not yet been fully identified. Here, we investigate whether past abundance changes, current range sizes and projected range shifts derived from species distribution models are related to plant trait values and intraspecific trait variation. We combined 17,921 trait records with observed past and modelled future distributions from 62 tundra shrub species across three continents. We found that species with greater variation in seed mass and specific leaf area had larger projected range shifts, and projected winner species had greater seed mass values. However, trait values and variation were not consistently related to current and projected ranges, nor to past abundance change. Overall, our findings indicate that abundance change and range shifts will not lead to directional modifications in shrub trait composition, since winner and loser species share relatively similar trait spaces. Functional trait data could guide predictions of species responses to environmental change. Here, the authors show that winner and loser shrub species in the warming tundra biome overlap in trait space and may therefore be difficult to predict based on commonly measured traits.
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- Björkman, Anne, 1981, et al.
(author)
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Plant functional trait change across a warming tundra biome
- 2018
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 562:7725, s. 57-62
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Journal article (peer-reviewed)abstract
- The tundra is warming more rapidly than any other biome on Earth, and the potential ramifications are far-reaching because of global feedback effects between vegetation and climate. A better understanding of how environmental factors shape plant structure and function is crucial for predicting the consequences of environmental change for ecosystem functioning. Here we explore the biome-wide relationships between temperature, moisture and seven key plant functional traits both across space and over three decades of warming at 117 tundra locations. Spatial temperature–trait relationships were generally strong but soil moisture had a marked influence on the strength and direction of these relationships, highlighting the potentially important influence of changes in water availability on future trait shifts in tundra plant communities. Community height increased with warming across all sites over the past three decades, but other traits lagged far behind predicted rates of change. Our findings highlight the challenge of using space-for-time substitution to predict the functional consequences of future warming and suggest that functions that are tied closely to plant height will experience the most rapid change. They also reveal the strength with which environmental factors shape biotic communities at the coldest extremes of the planet and will help to improve projections of functional changes in tundra ecosystems with climate warming.
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- Blach, S., et al.
(author)
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Hepatitis C Elimination in Sweden : Progress, Challenges and Opportunities for Growth in the time of COVID-19
- 2021
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In: Liver international. - : Wiley-Blackwell Publishing Inc.. - 1478-3223 .- 1478-3231. ; 41:9, s. 2024-2031
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Journal article (peer-reviewed)abstract
- BACKGROUND & AIMS: In 2014, the burden of hepatitis C virus (HCV) in Sweden was evaluated, to establish a baseline and inform public health interventions. Considering the changing landscape of HCV treatment, prevention, and care, and in light of the COVID-19 pandemic, this analysis seeks to evaluate Sweden's progress toward the WHO elimination targets and identify remaining barriers.METHODS: The data used for modeling HCV transmission and disease burden in Sweden were obtained through literature review, unpublished sources, and expert input. A dynamic Markov model was employed to forecast population sizes and incidence of HCV through 2030. Two scenarios ("2019 Base" and "WHO Targets") were developed to evaluate Sweden's progress toward HCV elimination.RESULTS: At the beginning of 2019, there were 29,700 (95% UI: 19,300 - 33,700) viremic infections in Sweden. Under the base scenario, Sweden would achieve and exceed the WHO targets for diagnosis, treatment, and liver-related death. However, new infections would decrease by less than 10%, relative to 2015. Achieving all WHO targets by 2030 would require 1) expanding harm reduction programs to reach more than 90% of PWID and 2) treating 90% of HCV+ PWID engaged in harm reduction programs and ≥7% of PWID not involved in harm reduction programs, annually by 2025.CONCLUSIONS: It is of utmost importance that Sweden, and all countries, find sustainability in HCV programs by broadening the setting and base of providers to provide stability and continuity of care during turbulent times.
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- Eriksson, Mikael, et al.
(author)
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Benefit of pazopanib in advanced gastrointestinal stromal tumours: results from a phase II trial (SSG XXI, PAGIST)
- 2021
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In: ESMO Open. - : Elsevier BV. - 2059-7029. ; 6:4
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Journal article (peer-reviewed)abstract
- BACKGROUND: Patients with advanced gastrointestinal stromal tumours (GISTs) resistant to the tyrosine kinase inhibitors imatinib and sunitinib may be treated with regorafenib, which resulted in a median progression-free survival (PFS) of 4.8 months in the GRID trial. Also, pazopanib, another tyrosine kinase inhibitor, has been studied in a randomized, placebo-controlled trial (PAZOGIST) in the third line, which showed a PFS of 45.2% 4 months after study entry, but patients intolerant to sunitinib were also included. We designed another trial evaluating pazopanib, enrolling only patients with progression on both imatinib and sunitinib. PATIENTS AND METHODS: Since all eligible patients had progressive disease, we preferred a non-randomized, phase II multicentre trial so that all patients could receive a potentially active drug. Patients had a progressive metastatic or locally advanced GIST and were ≥18 years of age, with a performance status of 0-2, and sufficient organ functions. The primary endpoint was disease control rate (defined as complete remission + partial remission + stable disease) at 12 weeks on pazopanib. A Simon's two-stage analysis was used with an interim analysis 12 weeks after enrollment of the first 22 patients, and if passed, there was a full enrolment of 72 patients. GIST mutational analysis was done, and most patients had pazopanib plasma concentration measured after 12 weeks. RESULTS: Seventy-two patients were enrolled. The disease control rate after 12 weeks was 44%, and the median PFS was 19.6 weeks (95% confidence interval 12.6-23.4 weeks). Pazopanib-related toxicity was moderate and manageable. No statistically significant differences were found related to mutations. Plasma concentrations of pazopanib had a formal but weak correlation with outcome. CONCLUSION: Pazopanib given in the third line to patients with GIST progressing on both imatinib and sunitinib was beneficial for about half of the patients. The PAGIST trial confirms the results from the PAZOGIST trial, and the median PFS achieved seems comparable to the PFS achieved with regorafenib in the third-line setting.
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| 18. |
- von Oppen, J., et al.
(author)
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Annual air temperature variability and biotic interactions explain tundra shrub species abundance
- 2021
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In: Journal of Vegetation Science. - : Wiley. - 1100-9233 .- 1654-1103. ; 32:2
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Journal article (peer-reviewed)abstract
- Questions Shrub vegetation has been expanding across much of the rapidly changing Arctic. Yet, there is still uncertainty about the underlying drivers of shrub community composition. Here, we use extensive vegetation surveys and a trait-based approach to answer the following questions: which abiotic and biotic factors explain abundance of shrub species and functional groups in the Arctic tundra, and can we interpret these relationships using plant traits related to resource acquisition? Location Nuup Kangerlua (Godthabsfjord), western Greenland. Methods We tested the power of nine climatic, topographic and biotic variables to explain the abundances of nine shrub species using a Bayesian hierarchical modelling framework. Results We found highly variable responses among species and functional groups to both abiotic and biotic environmental variation. The overall most important abiotic explanatory variable was annual air temperature variability, which was highly correlated with winter minimum air temperature. Functional community composition and graminoid abundance were the most influential biotic factors. While we did not find systematic patterns between shrub abundances and abiotic variables with regard to resource acquisition traits, these traits did explain relationships between shrub abundances and biotic variables. Conclusions Shrub abundance responses to abiotic variables rarely aligned with expectations based on plants' resource acquisition traits or functional groups. Our results, therefore, indicate that approaches exclusively based on resource acquisition traits might be limited in their ability to predict abundances of individual groups and species, particularly in response to complex abiotic environments. However, integrating community theory and functional trait concepts represents a promising pathway to better predict biotic interactions and ultimately responses of dominant shrub vegetation to rapid environmental changes across the arctic tundra biome.
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