| 1. |
- Christensen, Steffen, et al.
(author)
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Preadmission statin use and one-year mortality among patients in intensive care : a cohort study
- 2010
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In: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535 .- 1466-609X. ; 14:2, s. R29-
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Statins reduce risk of cardiovascular events and have beneficial pleiotropic effects; both may reduce mortality in critically ill patients. We examined whether statin use was associated with risk of death in general intensive care unit (ICU) patients. METHODS: Cohort study of 12,483 critically ill patients > 45 yrs of age with a first-time admission to one of three highly specialized ICUs within the Aarhus University Hospital network, Denmark, between 2001 and 2007. Statin users were identified through population-based prescription databases. We computed cumulative mortality rates 0-30 days and 31-365 days after ICU admission and mortality rate ratios (MRRs), using Cox regression analysis controlling for potential confounding factors (demographics, use of other cardiovascular drugs, comorbidity, markers of social status, diagnosis, and surgery). RESULTS: 1882 (14.3%) ICU patients were current statin users. Statin users had a reduced risk of death within 30 days of ICU admission [users: 22.1% vs. non-users 25.0%; adjusted MRR = 0.76 (95% confidence interval (CI): 0.69 to 0.86)]. Statin users also had a reduced risk of death within one year after admission to the ICU [users: 36.4% vs. non-users 39.9%; adjusted MRR = 0.79 (95% CI: 0.73 to 0.86)]. Reduced risk of death associated with current statin use remained robust in various subanalyses and in an analysis using propensity score matching. Former use of statins and current use of non-statin lipid-lowering drugs were not associated with reduced risk of death. CONCLUSIONS: Preadmission statin use was associated with reduced risk of death following intensive care. The associations seen could be a pharmacological effect of statins, but unmeasured differences in characteristics of statin users and non-users cannot be entirely ruled out.
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| 2. |
- Christensen, Steffen, et al.
(author)
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Three-year mortality among alcoholic patients after intensive care : a population-based cohort study
- 2012
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In: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535 .- 1466-609X. ; 16:1, s. R5-
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Journal article (peer-reviewed)abstract
- Introduction: Alcoholic patients comprise a large proportion of patients in intensive care units (ICUs). However, data are limited on the impact of alcoholism on mortality after intensive care. Methods: We conducted a cohort study among 16,848 first-time ICU patients between 2001 and 2007 to examine 30-day and 3-year mortality among alcoholic patients. Alcoholic patients with and without complications of alcohol misuse (for example, alcoholic liver disease) were identified from previous hospital contacts for alcoholism-related conditions or redemption of a prescription for alcohol deterrents. Data on medication use, demographics, hospital diagnoses, and comorbidity were obtained from medical databases. We computed 30-day and 3-year mortality and mortality rate ratios (MRRs) by using Cox regression analysis, controlling for covariates. Results: In total, 1,229 (7.3%) ICU patients were current alcoholics. Among alcoholic patients without complications of alcoholism (n = 785, 4.7% of the cohort), 30-day mortality was 15.9% compared with 19.7% among nonalcoholic patients. Compared with nonalcoholic patients, the adjusted 30-day MRR was 1.04 (95% confidence interval (CI), 0.87 to 1.25). Three-year mortality was 36.2% compared with 40.9% among nonalcoholic patients, corresponding to an adjusted 3-year MRR of 1.16 (95% CI, 1.03 to 1.31). For alcoholic patients with complications (n = 444, 2.6% of the cohort), 30-day mortality was 33.6%, and 3-year mortality was 64.5%, corresponding to adjusted MRRs, with nonalcoholics as the comparator, of 1.64 (95% CI, 1.38 to 1.95) and 1.67 (95% CI, 1.48 to 1.90), respectively. Conclusions: Alcoholic ICU patients with chronic complications of alcoholism have substantially increased 30-day and 3-year mortality. In contrast, alcoholics without complications have no increased 30-day and only slightly increased 3-year mortality.
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| 3. |
- Chung, Jaeyoon, et al.
(author)
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Genome-wide association study of cerebral small vessel disease reveals established and novel loci
- 2019
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In: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 142:10, s. 3176-3189
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Journal article (peer-reviewed)abstract
- Intracerebral haemorrhage and small vessel ischaemic stroke (SVS) are the most acute manifestations of cerebral small vessel disease, with no established preventive approaches beyond hypertension management. Combined genome-wide association study (GWAS) of these two correlated diseases may improve statistical power to detect novel genetic factors for cerebral small vessel disease, elucidating underlying disease mechanisms that may form the basis for future treatments. Because intracerebral haemorrhage location is an adequate surrogate for distinct histopathological variants of cerebral small vessel disease (lobar for cerebral amyloid angiopathy and non-lobar for arteriolosclerosis), we performed GWAS of intracerebral haemorrhage by location in 1813 subjects (755 lobar and 1005 non-lobar) and 1711 stroke-free control subjects. Intracerebral haemorrhage GWAS results by location were meta-analysed with GWAS results for SVS from MEGASTROKE, using 'Multi-Trait Analysis of GWAS' (MTAG) to integrate summary data across traits and generate combined effect estimates. After combining intracerebral haemorrhage and SVS datasets, our sample size included 241 024 participants (6255 intracerebral haemorrhage or SVS cases and 233 058 control subjects). Genome-wide significant associations were observed for non-lobar intracerebral haemorrhage enhanced by SVS with rs2758605 [MTAG P-value (P) = 2.6 × 10-8] at 1q22; rs72932727 (P = 1.7 × 10-8) at 2q33; and rs9515201 (P = 5.3 × 10-10) at 13q34. In the GTEx gene expression library, rs2758605 (1q22), rs72932727 (2q33) and rs9515201 (13q34) are significant cis-eQTLs for PMF1 (P = 1 × 10-4 in tibial nerve), NBEAL1, FAM117B and CARF (P < 2.1 × 10-7 in arteries) and COL4A2 and COL4A1 (P < 0.01 in brain putamen), respectively. Leveraging S-PrediXcan for gene-based association testing with the predicted expression models in tissues related with nerve, artery, and non-lobar brain, we found that experiment-wide significant (P < 8.5 × 10-7) associations at three genes at 2q33 including NBEAL1, FAM117B and WDR12 and genome-wide significant associations at two genes including ICA1L at 2q33 and ZCCHC14 at 16q24. Brain cell-type specific expression profiling libraries reveal that SEMA4A, SLC25A44 and PMF1 at 1q22 and COL4A1 and COL4A2 at 13q34 were mainly expressed in endothelial cells, while the genes at 2q33 (FAM117B, CARF and NBEAL1) were expressed in various cell types including astrocytes, oligodendrocytes and neurons. Our cross-phenotype genetic study of intracerebral haemorrhage and SVS demonstrates novel genome-wide associations for non-lobar intracerebral haemorrhage at 2q33 and 13q34. Our replication of the 1q22 locus previous seen in traditional GWAS of intracerebral haemorrhage, as well as the rediscovery of 13q34, which had previously been reported in candidate gene studies with other cerebral small vessel disease-related traits strengthens the credibility of applying this novel genome-wide approach across intracerebral haemorrhage and SVS.
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| 4. |
- Egg, David, et al.
(author)
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Therapeutic options for CTLA-4 insufficiency
- 2022
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In: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 149:2, s. 736-746
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Journal article (peer-reviewed)abstract
- Background: Heterozygous germline mutations in cytotoxic T lymphocyte-associated antigen-4 (CTLA4) impair the immunomodulatory function of regulatory T cells. Affected individuals are prone to life-threatening autoimmune and lymphoproliferative complications. A number of therapeutic options are currently being used with variable effectiveness. Objective: Our aim was to characterize the responsiveness of patients with CTLA-4 insufficiency to specific therapies and provide recommendations for the diagnostic workup and therapy at an organ-specific level. Methods: Clinical features, laboratory findings, and response to treatment were reviewed retrospectively in an international cohort of 173 carriers of CTLA4 mutation. Patients were followed between 2014 and 2020 for a total of 2624 months from diagnosis. Clinical manifestations were grouped on the basis of organ-specific involvement. Medication use and response were recorded and evaluated. Results: Among the 173 CTLA4 mutation carriers, 123 (71%) had been treated for immune complications. Abatacept, rituximab, sirolimus, and corticosteroids ameliorated disease severity, especially in cases of cytopenias and lymphocytic organ infiltration of the gut, lungs, and central nervous system. Immunoglobulin replacement was effective in prevention of infection. Only 4 of 16 patients (25%) with cytopenia who underwent splenectomy had a sustained clinical response. Cure was achieved with stem cell transplantation in 13 of 18 patients (72%). As a result of the aforementioned methods, organ-specific treatment pathways were developed. Conclusion: Systemic immunosuppressants and abatacept may provide partial control but require ongoing administration. Allogeneic hematopoietic stem cell transplantation offers a possible cure for patients with CTLA-4 insufficiency.
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| 5. |
- Head, Martin J., et al.
(author)
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The Great Acceleration is real and provides a quantitative basis for the proposed Anthropocene Series/Epoch
- 2022
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In: Episodes. - : International Union of Geological Sciences. - 0705-3797 .- 2586-1298. ; 45:4, s. 359-376
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Journal article (peer-reviewed)abstract
- The Anthropocene was conceptualized in 2000 to reflect the extensive impact of human activities on our planet, and subsequent detailed analyses have revealed a substantial Earth System response to these impacts beginning in the mid-20th century. Key to this understanding was the discovery of a sharp upturn in a multitude of global socio-economic indicators and Earth System trends at that time; a phenomenon termed the ‘Great Acceleration’. It coincides with massive increases in global human-consumed energy and shows the Earth System now on a trajectory far exceeding the earlier variability of the Holocene Epoch, and in some respects the entire Quaternary Period. The evaluation of geological signals similarly shows the mid-20th century as representing the most appropriate inception for the Anthropocene. A recent mathematical analysis has nonetheless challenged the significance of the original Great Acceleration data. We examine this analytical approach and reiterate the robustness of the original data in supporting the Great Acceleration, while emphasizing that intervals of rapid growth are inevitably time-limited, as recognised at the outset. Moreover, the exceptional magnitude of this growth remains undeniable, reaffirming the centrality of the Great Acceleration in justifying a formal chronostratigraphic Anthropocene at the rank of series/epoch.
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| 6. |
- Parmar, Divya, et al.
(author)
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Does community-based health insurance protect household assets? Evidence from rural Africa
- 2012
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In: Health Services Research. - : Wiley. - 0017-9124 .- 1475-6773. ; 47:2, s. 819-839
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To evaluate whether community-based health insurance (CBHI) protects household assets in rural Burkina Faso, Africa. DATA SOURCES: Data were used from a household panel survey that collected primary data from randomly selected households, covering 41 villages and one town, during 2004-2007(n = 890). STUDY DESIGN: The study area was divided into 33 clusters and CBHI was randomly offered to these clusters during 2004-2006. We applied different strategies to control for selection bias-ordinary least squares with covariates, two-stage least squares with instrumental variable, and fixed-effects models. DATA COLLECTION: Household members were interviewed in their local language every year, and information was collected on demographic and socio-economic indicators including ownership of assets, and on self-reported morbidity. PRINCIPAL FINDINGS: Fixed-effects and ordinary least squares models showed that CBHI protected household assets during 2004-2007. The two-stage least squares with instrumental variable model showed that CBHI increased household assets during 2004-2005. CONCLUSIONS: In this study, we found that CBHI has the potential to not only protect household assets but also increase household assets. However, similar studies from developing countries that evaluate the impact of health insurance on household economic indicators are needed to benchmark these results with other settings.
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| 7. |
- Steffen, Will, et al.
(author)
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Stratigraphic and Earth System approaches to defining the Anthropocene
- 2016
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In: Earth's Future. - 2328-4277. ; 4:8, s. 324-345
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Research review (peer-reviewed)abstract
- Stratigraphy provides insights into the evolution and dynamics of the Earth System over its long history. With recent developments in Earth System science, changes in Earth System dynamics can now be observed directly and projected into the near future. An integration of the two approaches provides powerful insights into the nature and significance of contemporary changes to Earth. From both perspectives, the Earth has been pushed out of the Holocene Epoch by human activities, with the mid-20th century a strong candidate for the start date of the Anthropocene, the proposed new epoch in Earth history. Here we explore two contrasting scenarios for the future of the Anthropocene, recognizing that the Earth System has already undergone a substantial transition away from the Holocene state. A rapid shift of societies toward the UN Sustainable Development Goals could stabilize the Earth System in a state with more intense interglacial conditions than in the late Quaternary climate regime and with little further biospheric change. In contrast, a continuation of the present Anthropocene trajectory of growing human pressures will likely lead to biotic impoverishment and a much warmer climate with a significant loss of polar ice.
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| 8. |
- van den Berg, Gerard J., et al.
(author)
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Economic conditions and the health of newborns : Evidence from comprehensive register data
- 2020
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In: Labour Economics. - : Elsevier BV. - 0927-5371 .- 1879-1034. ; 63
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Journal article (peer-reviewed)abstract
- We examine whether economic downturns are beneficial to health outcomes of newborn infants in developed countries. For this we use merged population-wide registers on health and economic and demographic variables, including the national medical birth register and intergenerational link registers from Sweden covering 1992-2004. We take a rigorous econometric approach that exploits regional variation in unemployment and compares babies born to the same parents so as to deal with possible selective fertility based on labour market conditions. We find that downturns are beneficial; an increase in the unemployment rate during pregnancy reduces the probability of having a birth weight less than 1500 grams or of dying within 28 days of birth. Effects are larger in low socio-economic status households. Health improvements cannot be attributed to the parents' own employment status. Instead, the results suggest other pathways triggered by the economic cycle.
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