1. |
- Ademuyiwa, Adesoji O., et al.
(author)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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In: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Journal article (peer-reviewed)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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2. |
- Beal, Jacob, et al.
(author)
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Robust estimation of bacterial cell count from optical density
- 2020
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Journal article (peer-reviewed)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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3. |
- Abbafati, Cristiana, et al.
(author)
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- 2020
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Journal article (peer-reviewed)
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4. |
- Efferth, Thomas, et al.
(author)
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Biopiracy versus One-World Medicine-From colonial relicts to global collaborative concepts
- 2019
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In: Phytomedicine. - : Elsevier. - 0944-7113 .- 1618-095X. ; 53, s. 319-331
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Research review (peer-reviewed)abstract
- Background: Practices of biopiracy to use genetic resources and indigenous knowledge by Western companies without benefit-sharing of those, who generated the traditional knowledge, can be understood as form of neo-colonialism. Hypothesis: The One-World Medicine concept attempts to merge the best of traditional medicine from developing countries and conventional Western medicine for the sake of patients around the globe. Study design: Based on literature searches in several databases, a concept paper has been written. Legislative initiatives of the United Nations culminated in the Nagoya protocol aim to protect traditional knowledge and regulate benefit-sharing with indigenous communities. The European community adopted the Nagoya protocol, and the corresponding regulations will be implemented into national legislation among the member states. Despite pleasing progress, infrastructural problems of the health care systems in developing countries still remain. Current approaches to secure primary health care offer only fragmentary solutions at best. Conventional medicine from industrialized countries cannot be afforded by the impoverished population in the Third World. Confronted with exploding costs, even health systems in Western countries are endangered to burst. Complementary and alternative medicine (CAM) is popular among the general public in industrialized countries, although the efficacy is not sufficiently proven according to the standards of evidence-based medicine. CAM is often available without prescription as over-the-counter products with non-calculated risks concerning erroneous self-medication and safety/toxicity issues. The concept of integrative medicine attempts to combine holistic CAM approaches with evidence-based principles of conventional medicine. Conclusion: To realize the concept of One-World Medicine, a number of standards have to be set to assure safety, efficacy and applicability of traditional medicine, e.g. sustainable production and quality control of herbal products, performance of placebo-controlled, double-blind, randomized clinical trials, phytovigilance, as well as education of health professionals and patients.
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5. |
- Murray, Christopher J. L., et al.
(author)
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Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
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In: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1995-2051
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Journal article (peer-reviewed)abstract
- Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49·4% (95% uncertainty interval [UI] 46·4–52·0). The TFR decreased from 4·7 livebirths (4·5–4·9) to 2·4 livebirths (2·2–2·5), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83·8 million people per year since 1985. The global population increased by 197·2% (193·3–200·8) since 1950, from 2·6 billion (2·5–2·6) to 7·6 billion (7·4–7·9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2·0%; this rate then remained nearly constant until 1970 and then decreased to 1·1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2·5% in 1963 to 0·7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2·7%. The global average age increased from 26·6 years in 1950 to 32·1 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59·9% to 65·3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1·0 livebirths (95% UI 0·9–1·2) in Cyprus to a high of 7·1 livebirths (6·8–7·4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0·08 livebirths (0·07–0·09) in South Korea to 2·4 livebirths (2·2–2·6) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0·3 livebirths (0·3–0·4) in Puerto Rico to a high of 3·1 livebirths (3·0–3·2) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2·0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill & Melinda Gates Foundation.
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9. |
- Amzaleg, Y., et al.
(author)
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Estrogens and selective estrogen receptor modulators differentially antagonize Runx2 in ST2 mesenchymal progenitor cells
- 2018
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In: Journal of Steroid Biochemistry and Molecular Biology. - : Elsevier BV. - 0960-0760 .- 1879-1220. ; 183, s. 10-17
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Journal article (peer-reviewed)abstract
- Estrogens attenuate bone turnover by inhibiting both osteoclasts and osteoblasts, in part through antagonizing Runx2. Apparently conflicting, stimulatory effects in osteoblast lineage cells, however, sway the balance between bone resorption and bone formation in favor of the latter. Consistent with this dualism, 17 beta-estradiol (E2) both stimulates and inhibits Runx2 in a locus-specific manner, and here we provide evidence for such locus specific regulation of Runx2 by E2 in vivo. We also demonstrate dual, negative and positive, regulation of Runx2-driven alkaline phosphatase (ALP) activity by increasing E2 concentrations in ST2 osteoblast progenitor cells. We further compared the effects of E2 to those of the Selective Estrogen Receptor Modulators (SERMs) raloxifene (ral) and lasofoxifene (las) and the phytoestrogen puerarin. We found that E2 at the physiological concentrations of 0.1-1 nM, as well as ral and las, but not puerarin, antagonize Runx2-driven ALP activity. At >= 10 nM, E2 and puerarin, but not ral or las, stimulate ALP relative to the activity measured at 0.1-1 nM. Contrasting the difference between E2 and SERMs in ST2 cells, they all shared a similar dose-response profile when inhibiting preosteoclast proliferation. That ral and las poorly mimic the locus-and concentration-dependent effects of E2 in mesenchymal progenitor cells may help explain their limited clinical efficacy.
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10. |
- Buchbinder, David, et al.
(author)
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Predictors of Loss to Follow-Up Among Pediatric and Adult Hematopoietic Cell Transplantation Survivors : A Report from the Center for International Blood and Marrow Transplant Research
- 2020
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In: Biology of blood and marrow transplantation. - : Elsevier. - 1083-8791 .- 1523-6536. ; 26:3, s. 553-561
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Journal article (peer-reviewed)abstract
- Follow-up is integral for hematopoietic cell transplantation (HCT) care to ensure surveillance and intervention for complications. We characterized the incidence of and predictors for being lost to follow-up. Two-year survivors of first allogeneic HCT (10,367 adults and 3865 children) or autologous HCT (7291 adults and 467 children) for malignant/nonmalignant disorders between 2002 and 2013 reported to the Center for International Blood and Marrow Transplant Research were selected. The cumulative incidence of being lost to follow-up (defined as having missed 2 consecutive follow-up reporting periods) was calculated. Marginal Cox models (adjusted for center effect) were fit to evaluate predictors. The 10-year cumulative incidence of being lost to follow-up was 13% (95% confidence interval [CI], 12% to 14%) in adult allogeneic HCT survivors, 15% (95% CI, 14% to 16%) in adult autologous HCT survivors, 25% (95% CI, 24% to 27%) in pediatric allogeneic HCT survivors, and 24% (95% CI, 20% to 29%) in pediatric autologous HCT survivors. Factors associated with being lost to follow-up include younger age, nonmalignant disease, public/no insurance (reference: private), residence farther from the tranplantation center, and being unmarried in adult allogeneic HCT survivors; older age and testicular/germ cell tumor (reference: non-Hodgkin lymphoma) in adult autologous HCT survivors; older age, public/no insurance (reference: private), and nonmalignant disease in pediatric allogeneic HCT survivors; and older age in pediatric autologous HCT survivors. Follow-up focusing on minimizing attrition in high-risk groups is needed to ensure surveillance for late effects.
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11. |
- Eklund, Anders, et al.
(author)
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The Pressure Difference between Eye and Brain Changes with Posture
- 2016
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In: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 80:2, s. 269-276
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Journal article (peer-reviewed)abstract
- Objective: The discovery of a posture-dependent effect on the difference between intraocular pressure (IOP) and intracranial pressure (ICP) at the level of lamina cribrosa could have important implications for understanding glaucoma and idiopathic intracranial hypertension and could help explain visual impairments in astronauts exposed to microgravity. The aim of this study was to determine the postural influence on the difference between simultaneously measured ICP and IOP.Methods: Eleven healthy adult volunteers (age = 46 ± 10 years) were investigated with simultaneous ICP, assessed through lumbar puncture, and IOP measurements when supine, sitting, and in 9° head-down tilt (HDT). The trans–lamina cribrosa pressure difference (TLCPD) was calculated as the difference between the IOP and ICP. To estimate the pressures at the lamina cribrosa, geometrical distances were estimated from magnetic resonance imaging and used to adjust for hydrostatic effects.Results: The TLCPD (in millimeters of mercury) between IOP and ICP was 12.3 ± 2.2 for supine, 19.8 ± 4.6 for sitting, and 6.6 ± 2.5 for HDT. The expected 24-hour average TLCPD on earth—assuming 8 hours supine and 16 hours upright—was estimated to be 17.3mmHg. By removing the hydrostatic effects on pressure, a corresponding 24-hour average TLCPD in microgravity environment was simulated to be 6.7mmHg.Interpretation: We provide a possible physiological explanation for how microgravity can cause symptoms similar to those seen in patients with elevated ICP. The observed posture dependency of TLCPD also implies that assessment of the difference between IOP and ICP in upright position may offer new understanding of the pathophysiology of idiopathic intracranial hypertension and glaucoma.
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12. |
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13. |
- Holmlund, Petter, et al.
(author)
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Human jugular vein collapse in the upright posture : implications for postural intracranial pressure regulation
- 2017
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In: Fluids and Barriers of the CNS. - : BioMed Central. - 2045-8118. ; 14
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Journal article (peer-reviewed)abstract
- Background: Intracranial pressure (ICP) is directly related to cranial dural venous pressure (P-dural). In the upright posture, P-dural is affected by the collapse of the internal jugular veins (IJVs) but this regulation of the venous pressure has not been fully understood. A potential biomechanical description of this regulation involves a transmission of surrounding atmospheric pressure to the internal venous pressure of the collapsed IJVs. This can be accomplished if hydrostatic effects are cancelled by the viscous losses in these collapsed veins, resulting in specific IJV cross-sectional areas that can be predicted from flow velocity and vessel inclination. Methods: We evaluated this potential mechanism in vivo by comparing predicted area to measured IJV area in healthy subjects. Seventeen healthy volunteers (age 45 +/- 9 years) were examined using ultrasound to assess IJV area and flow velocity. Ultrasound measurements were performed in supine and sitting positions. Results: IJV area was 94.5 mm(2) in supine and decreased to 6.5 +/- 5.1 mm(2) in sitting position, which agreed with the predicted IJV area of 8.7 +/- 5.2 mm(2) (equivalence limit +/- 5 mm(2), one-sided t tests, p = 0.03, 33 IJVs). Conclusions: The agreement between predicted and measured IJV area in sitting supports the occurrence of a hydrostatic-viscous pressure balance in the IJVs, which would result in a constant pressure segment in these collapsed veins, corresponding to a zero transmural pressure. This balance could thus serve as the mechanism by which collapse of the IJVs regulates P-dural and consequently ICP in the upright posture.
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14. |
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15. |
- Hori, Yasunori, et al.
(author)
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The Discovery and Follow-up of Four Transiting Short-period Sub-Neptunes Orbiting M Dwarfs
- 2024
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In: Astronomical Journal. - 1538-3881 .- 0004-6256. ; 167:6
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Journal article (peer-reviewed)abstract
- Sub-Neptunes with radii of 2-3 R ⊕ are intermediate in size between rocky planets and Neptune-sized planets. The orbital properties and bulk compositions of transiting sub-Neptunes provide clues to the formation and evolution of close-in small planets. In this paper, we present the discovery and follow-up of four sub-Neptunes orbiting M dwarfs (TOI-782, TOI-1448, TOI-2120, and TOI-2406), three of which were newly validated by ground-based follow-up observations and statistical analyses. TOI-782 b, TOI-1448 b, TOI-2120 b, and TOI-2406 b have radii of R p = 2.740 − 0.079 + 0.082 R ⊕ , 2.769 − 0.068 + 0.073 R ⊕ , 2.120 ± 0.067 R ⊕, and 2.830 − 0.066 + 0.068 R ⊕ and orbital periods of P = 8.02, 8.11, 5.80, and 3.08 days, respectively. Doppler monitoring with the Subaru/InfraRed Doppler instrument led to 2σ upper limits on the masses of <19.1 M ⊕, <19.5 M ⊕, <6.8 M ⊕, and <15.6 M ⊕ for TOI-782 b, TOI-1448 b, TOI-2120 b, and TOI-2406 b, respectively. The mass-radius relationship of these four sub-Neptunes testifies to the existence of volatile material in their interiors. These four sub-Neptunes, which are located above the so-called “radius valley,” are likely to retain a significant atmosphere and/or an icy mantle on the core, such as a water world. We find that at least three of the four sub-Neptunes (TOI-782 b, TOI-2120 b, and TOI-2406 b), orbiting M dwarfs older than 1 Gyr, are likely to have eccentricities of e ∼ 0.2-0.3. The fact that tidal circularization of their orbits is not achieved over 1 Gyr suggests inefficient tidal dissipation in their interiors.
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16. |
- Jóhannesson, Gauti, 1979-, et al.
(author)
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Intraocular Pressure Decrease Does Not Affect Blood Flow Rate of Ophthalmic Artery in Ocular Hypertension
- 2020
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In: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 61:12
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Journal article (peer-reviewed)abstract
- PURPOSE: To investigate if decrease of IOP affects the volumetric blood flow rate in the ophthalmic artery (OA) in patients with previously untreated ocular hypertension.METHODS: Subjects with untreated ocular hypertension (n = 30; mean age 67 +/- 8 years; 14 females) underwent ophthalmologic examination and a 3-Tesla magnetic resonance imaging investigation. The magnetic resonance imaging included three-dimensional high-resolution phase-contrast magnetic resonance imaging to measure the OA blood flow rate. The subjects received latanoprost once daily in the eye with higher pressure, the untreated eye served as control. The same measurements were repeated approximately 1 week later.RESULTS: The mean OA blood flow rate before and after treatment was 12.4 +/- 4.4 and 12.4 +/- 4.6 mL/min in the treated eye (mean +/- SD; P = 0.92) and 13.5 +/- 5.2 and 13.4 +/- 4.1 mL/min in the control eye (P = 0.92). There was no significant difference between the treated and control eye regarding blood flow rate before (P = 0.13) or after treatment (P = 0.18), or change in blood flow rate after treatment (0.1 +/- 3.1 vs.-0.1 +/- 4.0 mL/min, P = 0.84). Latanoprost decreased the IOP by 7.2 +/- 3.1 mm Hg in the treated eye (P < 0.01).CONCLUSIONS: The results indicate that a significant lowering of IOP does not affect the blood flow rate of the OA in ocular hypertension subjects. The ability to maintain blood supply to the eye independent of the IOP could be a protective mechanism in preserving vision in subjects with ocular hypertension.
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17. |
- Kassebaum, Nicholas J., et al.
(author)
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Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015 : a systematic analysis for the Global Burden of Disease Study 2015
- 2016
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In: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1603-1658
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Journal article (peer-reviewed)abstract
- Background Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate. Findings Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs off set by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2.9 years (95% uncertainty interval 2.9-3.0) for men and 3.5 years (3.4-3.7) for women, while HALE at age 65 years improved by 0.85 years (0.78-0.92) and 1.2 years (1.1-1.3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs. Interpretation Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum.
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18. |
- Klang, Marcus, et al.
(author)
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Hedwig : A named entity linker
- 2020
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In: LREC 2020 - 12th International Conference on Language Resources and Evaluation, Conference Proceedings. - 9791095546344 ; , s. 4501-4508
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Conference paper (peer-reviewed)abstract
- Named entity linking is the task of identifying mentions of named things in text, such as “Barack Obama” or “New York”, and linking these mentions to unique identifiers. In this paper, we describe Hedwig, an end-to-end named entity linker, which uses a combination of word and character BILSTM models for mention detection, a Wikidata and Wikipedia-derived knowledge base with global information aggregated over nine language editions, and a PageRank algorithm for entity linking. We evaluated Hedwig on the TAC2017 dataset, consisting of news texts and discussion forums, and we obtained a final score of 59.9% on CEAFmC+, an improvement over our previous generation linker Ugglan, and a trilingual entity link score of 71.9%.
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19. |
- Kostka, Kristin, et al.
(author)
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Unraveling COVID-19: A Large-Scale Characterization of 4.5 Million COVID-19 Cases Using CHARYBDIS.
- 2022
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In: Clinical epidemiology. - 1179-1349. ; 14, s. 369-384
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Journal article (peer-reviewed)abstract
- Routinely collected real world data (RWD) have great utility in aiding the novel coronavirus disease (COVID-19) pandemic response. Here we present the international Observational Health Data Sciences and Informatics (OHDSI) Characterizing Health Associated Risks and Your Baseline Disease In SARS-COV-2 (CHARYBDIS) framework for standardisation and analysis of COVID-19 RWD.We conducted a descriptive retrospective database study using a federated network of data partners in the United States, Europe (the Netherlands, Spain, the UK, Germany, France and Italy) and Asia (South Korea and China). The study protocol and analytical package were released on 11th June 2020 and are iteratively updated via GitHub. We identified three non-mutually exclusive cohorts of 4,537,153 individuals with a clinical COVID-19 diagnosis or positive test, 886,193 hospitalized with COVID-19, and 113,627 hospitalized with COVID-19 requiring intensive services.We aggregated over 22,000 unique characteristics describing patients with COVID-19. All comorbidities, symptoms, medications, and outcomes are described by cohort in aggregate counts and are readily available online. Globally, we observed similarities in the USA and Europe: more women diagnosed than men but more men hospitalized than women, most diagnosed cases between 25 and 60 years of age versus most hospitalized cases between 60 and 80 years of age. South Korea differed with more women than men hospitalized. Common comorbidities included type 2 diabetes, hypertension, chronic kidney disease and heart disease. Common presenting symptoms were dyspnea, cough and fever. Symptom data availability was more common in hospitalized cohorts than diagnosed.We constructed a global, multi-centre view to describe trends in COVID-19 progression, management and evolution over time. By characterising baseline variability in patients and geography, our work provides critical context that may otherwise be misconstrued as data quality issues. This is important as we perform studies on adverse events of special interest in COVID-19 vaccine surveillance.
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20. |
- Kristiansen, Martin, et al.
(author)
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Blood flow rate of ophthalmic artery in patients with normal tension glaucoma and healthy controls
- 2018
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In: Investigative Ophthalmology and Visual Science. - : The Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 59:9
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Journal article (other academic/artistic)abstract
- Purpose: To determine the blood flow rate of the ophthalmic artery (OA) in patients with Normal Tension Glaucoma (NTG) compared to age-matched healthy controls using phase-contrast magnetic resonance imaging (PCMRI).Methods: Seventeen patients with treated NTG (11 female; mean age: 70±9 years) and 16 age-matched healthy controls (10 female; mean age: 71±9 years) underwent PCMRI using a 3-Tesla scanner as well as ophthalmological examinations including visual acuity, Goldmann Applanation Tonometry, Humphrey perimetry and fundoscopy. Ophthalmic blood flow was acquired using a 2D PCMRI sequence set to a spatial resolution of 0.35mm/pixel. Mean flow rate and cross-sectional area was calculated using Segment Software. The eye with the most severe glaucomatous damage classified by visual field index (VFI) was chosen for comparison. The primary outcome was blood flow rate of OA.Results: The mean VFI was 41% ± 26 (mean±SD) for the worse NTG eyes. The intraocular pressure was 13.6±2.6 mmHg for NTG eyes and 13.8±2.1 mmHg for control eyes. The blood flow rate in the NTG group was 9.6±3.7 ml/min compared to 11.8±5.5 ml/min in the control group. The area was 1.7±0.3 mm2 and 2.0±0.6 mm2 respectively. No statistical significance was found between NTG and the control group regarding blood flow rate (p=0.07) or OA area (p=0.12).Conclusions: Despite OA being an anastomosis between the intracranial and extracranial circulation, possibly generating an eye unrelated variability in blood flow, we found a trend level reduction of approximately 2 ml/min in NTG. The finding warrants blood flow rate analysis of smaller arteries specifically supplying the eye, e.g. the central retinal artery.
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21. |
- Kristiansen, Martin, et al.
(author)
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Feasibility of MRI to assess differences in ophthalmic artery blood flow rate in normal tension glaucoma and healthy controls
- 2021
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In: Acta Ophthalmologica. - : John Wiley & Sons. - 1755-375X .- 1755-3768. ; 99:5, s. e679-e685
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Journal article (peer-reviewed)abstract
- Purpose: To examine feasibility of phase-contrast magnetic resonance imaging (PCMRI) and to assess blood flow rate in the ophthalmic artery (OA) in patients with normal tension glaucoma (NTG) compared with healthy controls.Methods: Sixteen patients with treated NTG and 16 age- and sex-matched healthy controls underwent PCMRI using a 3-Tesla scanner and ophthalmological examinations. OA blood flow rate was measured using a 2D PCMRI sequence with a spatial resolution of 0.35 mm(2).Results: The blood flow rate in the NTG group was 9.6 +/- 3.9 ml/min [mean +/- SD] compared with 11.9 +/- 4.8 ml/min in the control group. Resistance Index (RI) and Pulsatility Index (PI) were 0.73 +/- 0.08 and 1.36 +/- 0.29, respectively, in the NTG group and 0.68 +/- 0.13 and 1.22 +/- 0.40, respectively, in the healthy group. The mean visual field index (VFI) was 46% +/- 25 for the worse NTG eyes. The measured differences observed between the NTG group and the control group in blood flow rate (p = 0.12), RI (p = 0.18) and PI (p = 0.27) were non-significant.Conclusions: This case-control study, using PCMRI, showed a slight, but non-significant, reduction in OA blood flow rate in the NTG patients compared with the healthy controls. These results indicate that blood flow may be of importance in the pathogenesis of NTG. Considering that only a limited portion of the total OA blood flow supplies the ocular system and the large inter-individual differences, a larger study or more advanced PCMRI technique might give the answer.
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22. |
- Kölby, David, 1993, et al.
(author)
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Craniotomy of the Fused Sagittal Suture Over the Superior Sagittal Sinus Is a Safe Procedure
- 2017
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In: Journal of Craniofacial Surgery. - : Ovid Technologies (Wolters Kluwer Health). - 1049-2275. ; 28:3, s. 666-669
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Journal article (peer-reviewed)abstract
- Introduction: Spring-assisted cranioplasty to correct sagittal synostosis is based on midline craniotomy through the closed sagittal suture, over the superior sagittal sinus (SSS). The aim of the present study was to evaluate the perioperative safety of this technique. Materials and Methods: This is a retrospective study of all patients operated with median craniotomy and springs from 1998 to the end of 2015. For comparison, all Pi-plasties performed during the same time interval were also evaluated. The safety measures were evaluated based on incidence of damage to SSS, incidence of dural tears, perioperative blood loss, operative time, and hospital stay. Results: In the group that had undergone midline craniotomy combined with springs (n = 225), 4 perioperative damages to SSS and 1 dural tear were seen. The perioperative blood loss was 62.8 +/- 65.3mL (mean +/- standard deviation). The operative time was 67.9 +/- 21.5 minutes and the hospital stay was 4.8 +/- 1.1 days. In the group that had undergone pi-plasty (n = 105), no damages to SSS but 3 dural tears were seen. The perioperative blood loss was 352.8 +/- 174.4 mL. The operative time was 126.0 +/- 31.7 minutes and the hospital stay was 7.1 +/- 1.4 days. Conclusion: Craniotomy SSS in sagittal synostosis is a safe procedure with low morbidity in terms of damage to the SSS. Midline craniotomy combined with springs has significantly lower preoperative blood loss, operative time, and hospital stay (P < 0.001 for all) compared to pi-plasty.
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23. |
- Luciano, Mark G., et al.
(author)
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Epidural Oscillating Cardiac-Gated Intracranial Implant Modulates Cerebral Blood Flow
- 2020
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In: Neurosurgery. - : Oxford University Press. - 0148-396X .- 1524-4040. ; 87:6, s. 1299-1310
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Journal article (peer-reviewed)abstract
- Background: We have previously reported a method and device capable of manipulating ICP pulsatility while minimally effecting mean ICP.Objective: To test the hypothesis that different modulations of the intracranial pressure (ICP) pulse waveform will have a differential effect on cerebral blood flow (CBF).Methods: Using an epidural balloon catheter attached to a cardiac-gated oscillating pump, 13 canine subjects underwent ICP waveform manipulation comparing different sequences of oscillation in successive animals. The epidural balloon was implanted unilaterally superior to the Sylvian sulcus. Subjects underwent ICP pulse augmentation, reduction and inversion protocols, directly comparing time segments of system activation and deactivation. ICP and CBF were measured bilaterally along with systemic pressure and heart rate. CBF was measured using both thermal diffusion, and laser doppler probes.Results: The activation of the cardiac-gate balloon implant resulted in an ipsilateral/contralateral ICP pulse amplitude increase with augmentation (217%/202% respectively, P < .0005) and inversion (139%/120%, P < .0005). The observed changes associated with the ICP mean values were smaller, increasing with augmentation (23%/31%, P < .0001) while decreasing with inversion (7%/11%, P = .006/.0003) and reduction (4%/5%, P < .0005). CBF increase was observed for both inversion and reduction protocols (28%/7.4%, P < .0001/P = .006 and 2.4%/1.3%, P < .0001/P = .003), but not the augmentation protocol. The change in CBF was correlated with ICP pulse amplitude and systolic peak changes and not with change in mean ICP or systemic variables (heart rate, arterial blood pressure).Conclusion: Cardiac-gated manipulation of ICP pulsatility allows the study of intracranial pulsatile dynamics and provides a potential means of altering CBF.
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24. |
- Nugues, Pierre, et al.
(author)
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Connecting a French Dictionary from the Beginning of the 20th Century to Wikidata
- 2022
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In: 2022 Language Resources and Evaluation Conference, LREC 2022. - 9791095546726 ; , s. 2548-2555
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Conference paper (peer-reviewed)abstract
- The Petit Larousse illustré is a French dictionary first published in 1905. Its division in two main parts on language and on history and geography corresponds to a major milestone in French lexicography as well as a repository of general knowledge from this period. Although the value of many entries from 1905 remains intact, some descriptions now have a dimension that is more historical than contemporary. They are nonetheless significant to analyze and understand cultural representations from this time. A comparison with more recent information or a verification of these entries would require a tedious manual work. In this paper, we describe a new lexical resource, where we connected all the dictionary entries of the history and geography part to current data sources. For this, we linked each of these entries to a wikidata identifier. Using the wikidata links, we can automate more easily the identification, comparison, and verification of historically-situated representations. We give a few examples on how to process wikidata identifiers and we carried out a small analysis of the entities described in the dictionary to outline possible applications. The resource, i.e. the annotation of 20,245 dictionary entries with wikidata links, is available from GitHub (https://github.com/pnugues/petit_larousse_1905/).
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25. |
- Pineda-Moncusí, Marta, et al.
(author)
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Classification of patients with osteoarthritis through clusters of comorbidities using 633,330 individuals from Spain
- 2023
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In: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332. ; 62:11, s. 3592-3600
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: To explore clustering of comorbidities among patients with a new diagnosis of osteoarthritis (OA) and estimate the 10-year mortality risk for each identified cluster.METHODS: This is a population-based cohort study of individuals with first incident diagnosis of OA of the hip, knee, ankle/foot, wrist/hand, or 'unspecified' site between 2006 and 2020, using SIDIAP (a primary care database representative from Catalonia, Spain). At the time of OA diagnosis, conditions associated with OA in the literature that were found in ≥ 1% of the individuals (n = 35) were fitted into two cluster algorithms, K-means and latent class analysis (LCA). Models were assessed using a range of internal and external criteria evaluation procedures. Mortality risk of the obtained clusters was assessed by survival analysis using Cox proportional hazards.RESULTS: We identified 633 330 patients with a diagnosis of OA. Our proposed best solution used LCA to identify four clusters: 'Low-morbidity (relatively low number of comorbidities), 'Back/neck pain plus mental health', 'Metabolic syndrome' and 'Multimorbidity' (higher prevalence of all study comorbidities). Compared with the 'Low-morbidity, the 'Multimorbidity' cluster had the highest risk of 10-year mortality (adjusted HR: 2.19 [95%CI: 2.15-2.23]), followed by 'Metabolic syndrome' (adjusted HR: 1.24 [95%CI: 1.22-1.27]]) and 'Back/neck pain plus mental health' (adjusted HR: 1.12 [95%CI: 1.09-1.15]).CONCLUSION: Patients with a new diagnosis of OA can be clustered into groups based on their comorbidity profile, with significant differences in 10-year mortality risk. Further research is required to understand the interplay between OA and particular comorbidity groups, and the clinical significance of such results.
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26. |
- Prusakov, Pavel, et al.
(author)
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A global point prevalence survey of antimicrobial use in neonatal intensive care units : The no-more-antibiotics and resistance (NO-MAS-R) study
- 2021
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In: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 32
-
Journal article (peer-reviewed)abstract
- Background: Global assessment of antimicrobial agents prescribed to infants in the neonatal intensive care unit (NICU) may inform antimicrobial stewardship efforts.Methods: We conducted a one-day global point prevalence study of all antimicrobials provided to NICU infants. Demographic, clinical, and microbiologic data were obtained including NICU level, census, birth weight, gestational/chronologic age, diagnoses, antimicrobial therapy (reason for use; length of therapy), antimicrobial stewardship program (ASP), and 30-day in-hospital mortality.Findings: On July 1, 2019, 26% of infants (580/2,265; range, 0-100%; median gestational age, 33 weeks; median birth weight, 1800 g) in 84 NICUs (51, high-income; 33, low-to-middle income) from 29 countries (14, high-income; 15, low-to-middle income) in five continents received >= 1 antimicrobial agent (92%, antibacterial; 19%, antifungal; 4%, antiviral). The most common reasons for antibiotic therapy were "rule-out" sepsis (32%) and "culture-negative" sepsis (16%) with ampicillin (40%), gentamicin (35%), amikacin (19%), vancomycin (15%), and meropenem (9%) used most frequently. For definitive treatment of presumed/confirmed infection, vancomycin (26%), amikacin (20%), and meropenem (16%) were the most prescribed agents. Length of therapy for culture-positive and "culture-negative" infections was 12 days (median; IQR, 8-14) and 7 days (median; IQR, 5-10), respectively. Mortality was 6% (42%, infection-related). An NICU ASP was associated with lower rate of antibiotic utilization (p = 0.02).Interpretation: Global NICU antibiotic use was frequent and prolonged regardless of culture results. NICU-specific ASPs were associated with lower antibiotic utilization rates, suggesting the need for their implementation worldwide.
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27. |
- Qvarlander, Sara, et al.
(author)
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Cerebrospinal fluid and blood flow patterns in idiopathic normal pressure hydrocephalus
- 2017
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In: Acta Neurologica Scandinavica. - : Wiley-Blackwell. - 0001-6314 .- 1600-0404. ; 135:5, s. 576-584
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Journal article (peer-reviewed)abstract
- Objectives: Increased aqueduct cerebrospinal fluid (CSF) flow pulsatility and, recently, a reversed CSF flow in the aqueduct have been suggested as hallmarks of idiopathic normal pressure hydrocephalus (INPH). However, these findings have not been adequately confirmed. Our objective was to investigate the flow of blood and CSF in INPH, as compared to healthy elderly, in order to clarify which flow parameters are related to the INPH pathophysiology.Materials and Methods: Sixteen INPH patients (73 years) and 35 healthy subjects (72 years) underwent phase-contrast magnetic resonance imaging (MRI). Measurements included aqueduct and cervical CSF flow, total arterial inflow (tCBF; i.e. carotid + vertebral arteries), and internal jugular vein flow. Flow pulsatility, net flow, and flow delays were compared (multiple linear regression, correcting for sex and age).Results: Aqueduct stroke volume was higher in INPH than healthy (148±95 vs 90±50 mL, P<.05). Net aqueduct CSF flow was similar in magnitude and direction. The cervical CSF stroke volume was lower (P<.05). The internal carotid artery net flow was lower in INPH (P<.05), although tCBF was not. No differences were found in internal jugular vein flow or flow delays.Conclusions: The typical flow of blood and CSF in INPH was mainly characterized by increased CSF pulsatility in the aqueduct and reduced cervical CSF pulsatility. The direction of mean net aqueduct CSF flow was from the third to the fourth ventricle. Our findings may reflect the altered distribution of intracranial CSF volume in INPH, although the causality of these relationships is unclear.
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28. |
- Qvarlander, Sara, 1982-, et al.
(author)
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Differences in cerebral blood flow and CSF flow between INPH and healthy elderly
-
Other publication (other academic/artistic)abstract
- Idiopathic normal pressure hydrocephalus (INPH) is linked to disturbance of the CSF circulation, though the exact nature of the disturbance is not clarified. Phase contrast magnetic resonance imaging (PC-MRI) allows for measurement of local CSF and blood flows, and has been applied in hydrocephalus to demonstrate changes in both cerebral blood flow and aqueduct CSF flow. Many of these studies have, however been based on small numbers of subjects, or poorly defined selection criteria. This study therefore aimed to confirm if cerebral blood flow and CSF flow between compartments differed between INPH subjects and healthy elderly.Forty-three healthy elderly and 22 patients diagnosed with INPH according to the INPH guidelines were investigated with PC-MRI measurements of cerebral arterial inflow (CBF) and internal jugular venous outflow, cervical CSF flow, and aqueduct CSF flow. Both net flows, pulsatile aspects of flow, and delays between flow waveforms were analysed.Pulsatility in the aqueduct flow was significantly higher in INPH than healthy elderly (aqueduct stroke volume: 189±184 vs. 86±46 ml, p<0.01). There was larger variation in aqueduct net flow in INPH (SD: 1.31 vs. 0.25 ml/min), but the mean net flow did not differ. Cerebral blood flow and internal jugular vein flow showed no significant differences between the groups, though there was a trend toward lower CBF in the diastolic phase and higher CBF pulsatility index. No differences were found in flow delays.In conclusion, cerebral in- and outflow of blood, and cervical CSF flow were similar in healthy elderly and INPH subjects. Aqueduct flow showed higher pulsatility in INPH, but there was no general reversal of the direction of aqueduct net flow.
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29. |
- Rajwa, Pawel, et al.
(author)
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Research protocol for an observational health data analysis on the adverse events of systemic treatment in patients with metastatic hormone-sensitive prostate cancer : big data analytics using the PIONEER platform
- 2024
-
In: European Urology Open Science. - : Elsevier. - 2666-1691 .- 2666-1683. ; 63, s. 81-88
-
Journal article (peer-reviewed)abstract
- Combination therapies in metastatic hormone-sensitive prostate cancer (mHSPC), which include the addition of an androgen receptor signaling inhibitor and/or docetaxel to androgen deprivation therapy, have been a game changer in the management of this disease stage. However, these therapies come with their fair share of toxicities and side effects. The goal of this observational study is to report drug-related adverse events (AEs), which are correlated with systemic combination therapies for mHSPC. Determining the optimal treatment option requires large cohorts to estimate the tolerability and AEs of these combination therapies in “real-life” patients with mHSPC, as provided in this study. We use a network of databases that includes population-based registries, electronic health records, and insurance claims, containing the overall target population and subgroups of patients defined by unique certain characteristics, demographics, and comorbidities, to compute the incidence of common AEs associated with systemic therapies in the setting of mHSPC. These data sources are standardised using the Observational Medical Outcomes Partnership Common Data Model. We perform the descriptive statistics as well as calculate the AE incidence rate separately for each treatment group, stratified by age groups and index year. The time until the first event is estimated using the Kaplan-Meier method within each age group. In the case of episodic events, the anticipated mean cumulative counts of events are calculated. Our study will allow clinicians to tailor optimal therapies for mHSPC patients, and they will serve as a basis for comparative method studies.
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30. |
- Wang, Haidong, et al.
(author)
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Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015
- 2016
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In: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1459-1544
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Journal article (peer-reviewed)abstract
- BACKGROUND: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.METHODS: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).FINDINGS: Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4-61·9) in 1980 to 71·8 years (71·5-72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7-17·4), to 62·6 years (56·5-70·2). Total deaths increased by 4·1% (2·6-5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8-18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6-16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9-14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1-44·6), malaria (43·1%, 34·7-51·8), neonatal preterm birth complications (29·8%, 24·8-34·9), and maternal disorders (29·1%, 19·3-37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death.INTERPRETATION: At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems.
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31. |
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32. |
- Xie, Junqing, et al.
(author)
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Association of Tramadol vs Codeine Prescription Dispensation with Mortality and Other Adverse Clinical Outcomes
- 2021
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In: JAMA - Journal of the American Medical Association. - : American Medical Association (AMA). - 0098-7484. ; 326:15, s. 1504-1515
-
Journal article (peer-reviewed)abstract
- Importance: Although tramadol is increasingly used to manage chronic noncancer pain, few safety studies have compared it with other opioids. Objective: To assess the associations of tramadol, compared with codeine, with mortality and other adverse clinical outcomes as used in outpatient settings. Design, Setting, and Participants: Retrospective, population-based, propensity score-matched cohort study using a primary care database with routinely collected medical records and pharmacy dispensations covering more than 80% of the population of Catalonia, Spain (≈6 million people). Patients 18 years or older with 1 or more year of available data and dispensation of tramadol or codeine (2007-2017) were included and followed up to December 31, 2017. Exposures: New prescription dispensation of tramadol or codeine (no dispensation in the previous year). Main Outcomes and Measures: Outcomes studied were all-cause mortality, cardiovascular events, fractures, constipation, delirium, falls, opioid abuse/dependence, and sleep disorders within 1 year after the first dispensation. Absolute rate differences (ARDs) and hazard ratios (HRs) with 95% confidence intervals were calculated using cause-specific Cox models. Results: Of the 1093064 patients with a tramadol or codeine dispensation during the study period (326921 for tramadol, 762492 for codeine, 3651 for both drugs concomitantly), a total of 368960 patients (184480 propensity score-matched pairs) were included after study exclusions and propensity score matching (mean age, 53.1 [SD, 16.1] years; 57.3% women). Compared with codeine, tramadol dispensation was significantly associated with a higher risk of all-cause mortality (incidence, 13.00 vs 5.61 per 1000 person-years; HR, 2.31 [95% CI, 2.08-2.56]; ARD, 7.37 [95% CI, 6.09-8.78] per 1000 person-years), cardiovascular events (incidence, 10.03 vs 8.67 per 1000 person-years; HR, 1.15 [95% CI, 1.05-1.27]; ARD, 1.36 [95% CI, 0.45-2.36] per 1000 person-years), and fractures (incidence, 12.26 vs 8.13 per 1000 person-years; HR, 1.50 [95% CI, 1.37-1.65]; ARD, 4.10 [95% CI, 3.02-5.29] per 1000 person-years). No significant difference was observed for the risk of falls, delirium, constipation, opioid abuse/dependence, or sleep disorders. Conclusions and Relevance: In this population-based cohort study, a new prescription dispensation of tramadol, compared with codeine, was significantly associated with a higher risk of subsequent all-cause mortality, cardiovascular events, and fractures, but there was no significant difference in the risk of constipation, delirium, falls, opioid abuse/dependence, or sleep disorders. The findings should be interpreted cautiously, given the potential for residual confounding..
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33. |
- Xie, Junqing, et al.
(author)
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Trends of Dispensed Opioids in Catalonia, Spain, 2007–19 : A Population-Based Cohort Study of Over 5 Million Individuals
- 2022
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In: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 13
-
Journal article (peer-reviewed)abstract
- Objective: To characterize the trend of opioid use (number of users, dispensations and oral morphine milligram equivalents) in Catalonia (Spain). Design, setting, and participants: This population-based cohort study included all individuals aged 18 years or older, registered in the Information System for Research in Primary Care (SIDIAP), which covers >75% of the population in Catalonia, Spain, from 1 January 2007, to 31 December 2019. Main exposure and outcomes: The exposures were all commercialized opioids and their combinations (ATC-codes): codeine, tramadol, oxycodone, tapentadol, fentanyl, morphine, and other opioids (dihydrocodeine, hydromorphone, dextropropoxyphene, buprenorphine, pethidine, pentazocine). The main outcomes were the annual figures per 1,000 individuals of 1) opioid users, 2) dispensations, and 3) oral morphine milligram equivalents (MME). Results were stratified separately by opioid types, age (5-year age groups), sex (male or female), living area (rural or urban), and socioeconomic status (from least, U1, to most deprived, U5). The overall trends were quantified using the percentage change (PC) between 2007 and 2019. Results: Among 4,656,197 and 4,798,114 residents from 2007 to 2019, the number of opioid users, dispensations and morphine milligram equivalents per 1,000 individuals increased 12% (percentage change: 95% confidence interval (CI) 11.9–12.3%), 105% (95% confidence interval 83%–126%) and 339% (95% CI 289%–390%) respectively. Tramadol represented the majority of opioid use in 2019 (61, 59, and 54% of opioid users, dispensations, and total MME, respectively). Individuals aged 80 years or over reported the sharpest increase regarding opioid users (PC: 162%), dispensations (PC: 424%), and MME (PC: 830%). Strong opioids were increasingly prescribed for non-cancer pains over the years. Conclusion: Despite the modest increase of opioid users, opioid dispensations and MME increased substantially, particularly in the older population. In addition, strong opioids were incrementally indicated for non-cancer pains over the years. These findings suggest a transition of opioid prescriptions from intermittent to chronic and weak to strong and call for more rigorous opioid stewardship.
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34. |
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35. |
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- 2019
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Journal article (peer-reviewed)
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