Publications by authors named "Per Sandén"

12 Publications

  • Page 1 of 1

Chlorine cycling and the fate of Cl in terrestrial environments.

Environ Sci Pollut Res Int 2021 Feb 5;28(7):7691-7709. Epub 2021 Jan 5.

Department of Thematic Studies - Environmental Change, Linköping University, SE-581 83, Linkoping, Sweden.

Chlorine (Cl) in the terrestrial environment is of interest from multiple perspectives, including the use of chloride as a tracer for water flow and contaminant transport, organochlorine pollutants, Cl cycling, radioactive waste (radioecology; Cl is of large concern) and plant science (Cl as essential element for living plants). During the past decades, there has been a rapid development towards improved understanding of the terrestrial Cl cycle. There is a ubiquitous and extensive natural chlorination of organic matter in terrestrial ecosystems where naturally formed chlorinated organic compounds (Cl) in soil frequently exceed the abundance of chloride. Chloride dominates import and export from terrestrial ecosystems while soil Cl and biomass Cl can dominate the standing stock Cl. This has important implications for Cl transport, as chloride will enter the Cl pools resulting in prolonged residence times. Clearly, these pools must be considered separately in future monitoring programs addressing Cl cycling. Moreover, there are indications that (1) large amounts of Cl can accumulate in biomass, in some cases representing the main Cl pool; (2) emissions of volatile organic chlorines could be a significant export pathway of Cl and (3) that there is a production of Cl in tissues of, e.g. plants and animals and that Cl can accumulate as, e.g. chlorinated fatty acids in organisms. Yet, data focusing on ecosystem perspectives and combined spatiotemporal variability regarding various Cl pools are still scarce, and the processes and ecological roles of the extensive biological Cl cycling are still poorly understood.
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http://dx.doi.org/10.1007/s11356-020-12144-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854439PMC
February 2021

[ACE2 and coronavirus - a question of balance and dynamics?]

Lakartidningen 2020 04 17;117. Epub 2020 Apr 17.

med dr, biträdande överläkare, VO neurologi, Danderyds sjukhus; institutionen för kliniska vetenskaper, Danderyds sjukhus, Karolinska institutet.

The new SARS-CoV-2 virus enters cells via angiotensin-converting enzyme 2 (ACE2). ACE2 counteracts ACE and angiotensin II in the renin-angiotensin-aldosterone system (RAAS) and has critical functions in the lung and cardiovascular system. SARS-CoV was found to down-regulate ACE2, leaving angiotensin II unbalanced in affected organs.  A similar effect of SARS-CoV-2 could partly explain risk factors and symptoms, and could potentially be treatable.
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April 2020

Bleeding complications and mortality in warfarin-treated VTE patients, dependence of INR variability and iTTR.

Thromb Haemost 2017 01 22;117(1):27-32. Epub 2016 Sep 22.

Per Sandén, Department of Public Health and Clinical medicine, Umeå University, Sundsvall, Sweden, E-mail:

High quality of warfarin treatment is important to prevent recurrence of venous thromboembolism (VTE) without bleeding complications. The aim of this study was to examine the effect of individual time in therapeutic range (iTTR) and International Normalised Ratio (INR) variability on bleeding risk and mortality in a large cohort of well-managed patients with warfarin due to VTE. A cohort of 16612 patients corresponding to 19502 treatment periods with warfarin due to VTE between January 1, 2006 and December 31, 2011 was retrieved from the Swedish national quality register AuriculA and matched with the Swedish National Patient Register for bleeding complications and background characteristics and the Cause of death register for occurrence and date of death. The rate of bleeding was 1.79 (confidence interval (CI) 95 % 1.66-1.93) per 100 treatment years among all patients. Those with poor warfarin treatment quality had a higher rate of clinically relevant bleeding, both when measured as iTTR below 70 %, 2.91 (CI 95 % 2.61-3.21) or as INR variability over the mean value 0.85, 2.61 (CI 95 % 2.36-2.86). Among those with both high INR variability and low iTTR the risk of clinically relevant bleeding was clearly increased hazard ratio (HR) 3.47 (CI 95 % 2.89-4.17). A similar result was found for all-cause mortality with a HR of 3.67 (CI 95 % 3.02-4.47). Both a low iTTR and a high INR variability increase the risk of bleeding complications or mortality. When combining the two treatment quality indicators patients at particular high risk of bleeding or death can be identified.
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http://dx.doi.org/10.1160/TH16-06-0489DOI Listing
January 2017

Venous thromboembolism and cancer risk.

J Thromb Thrombolysis 2017 Jan;43(1):68-73

Department of Public Health and Clinical Medicine, Umeå University, Sundsvall, Sweden.

Cancer increases the risk of venous thromboembolism (VTE) and about 20 % of all VTE are associated with cancer. VTE can also be used as a marker for occult cancer. The objective was to examine the correlation between VTE and cancer regarding predictors for a subsequent cancer diagnosis. Patients treated for VTE between January 1st 2006 and December 31th 2011 were extracted from the Swedish national quality register AuriculA and crossmatched with the Swedish National Patient Register. In total 7854 patients corresponding to 14284 treatments years were examined. Primary VTE was found in 6451 patients, with 3936 first and 2515 recurrent VTE. There were 1403 patients with secondary VTE. After a first or recurrent primary VTE the incidence of cancer diagnose was high being 9.4-10.0 % the first year compared to 2.7-2.5 % during the second year. Cancer in the digestive organs was the most common type of cancer among those with first primary VTE with 19.2 % of diagnoses. In multivariable analysis age was found to increase the risk of cancer diagnosis after both first and recurrent primary VTE HR 1.02 (CI 1.02-1.03) and HR 1.02 (CI 1.01-1.03). For a first primary VTE anemia HR 2.13 (CI 1.48-3.08) and male sex HR 1.38 (CI 1.09-1.76) increased the risk while hypertension HR 0.74 (0.57-0.96), dementia HR 0.30 (CI 0.10-0.95) and history of major bleeding HR 0.52 (CI 0.28-0.97) reduced the risk of a subsequent cancer diagnosis. There is a substantial proportion of patients being diagnosed with cancer the first year after a primary VTE, anaemia and male sex confers an increased risk.
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http://dx.doi.org/10.1007/s11239-016-1411-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5233740PMC
January 2017

Bleeding complications in venous thrombosis patients on well-managed warfarin.

J Thromb Thrombolysis 2016 Feb;41(2):351-8

Department of Public Health and Clinical Medicine, Umeå University, Sundsvall, Sweden.

Anticoagulation treatment is effective in preventing both death and recurrence in patients with venous thromboembolism (VTE), but at the same time confers a substantial risk of bleeding complications. The aim of this study was to examine the rate of and predictors for bleeding complications in VTE patients on warfarin with high treatment quality. In total 13,859 patients on warfarin for VTE between January 1st 2006 and December 31th 2011 were retrieved from the national quality register Auricula. The cohort was matched with the Swedish National Patient Register for complications and background characteristics, the Cause of Death Register for date and cause of death and the Swedish Prescribed Drug Register for retrieved medication. The rate of major bleeding was 2.36 per 100 treatment years, increasing with age from 1.25 to 4.33 for those under 60 or over 80 years of age, respectively. Factors found to independently increase the risk of bleeding complications were increasing age HR 1.02, cardiac failure HR 1.39, Chronic pulmonary disease HR 1.41, alcohol abuse HR 3.33, anaemia HR 1.75, hypertension HR 1.29 and a history of major bleeding HR 1.69. Warfarin as treatment for VTE is safe with a low rate of bleeding complications at least for the younger patient. In an era of NOAK, warfarin has a comparable safety profile among VTE patients and is still a valid treatment option.
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http://dx.doi.org/10.1007/s11239-015-1305-4DOI Listing
February 2016

Warfarin treatment complications do not correlate to cTTR when above 70.

Thromb Res 2015 Dec 19;136(6):1185-9. Epub 2015 Oct 19.

Department of Public Health and Clinical medicine, Umeå University, Sundsvall, Sweden.

Background: The mean time in target range for each centre, cTTR, has previously been shown to correlate to the rate of complications in poorly managed warfarin treatment. However less is known about the correlation when warfarin treatment is well managed.

Objectives: The aim of this study was to examine the correlation between cTTR and the rate of complications in a real life setting with cTTR above 70%, with focus on patients with warfarin due to atrial fibrillation or secondary prevention of a VTE.

Patients/methods: In total 66,605 patients with 89,293 treatment periods, corresponding to 179,624 treatment years, with warfarin treatment due to VTE or AF between January 1st 2006 and December 31th 2011, was retrieved from the national quality register AuriculA. The cohort was matched with the National Patient Register in Sweden for complications and background characteristics.

Results: We found 172 centres and 68,797 treatment periods for AF and 166 centres and 20,496 treatment periods for VTE. Over 90% of the patients had a target range between INR 2-3. We found no correlation between increasing cTTR and reduction in the rate of complications for the AF patients. However, for VTE patients we saw a correlation between increasing cTTR and a reduced complication rate.

Conclusions: Our results show that at very high cTTR levels, above 70%, further improvements in cTTR do not correlate to less treatment complications at least for patients with AF.
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http://dx.doi.org/10.1016/j.thromres.2015.10.031DOI Listing
December 2015

Warfarin treatment quality is consistently high in both anticoagulation clinics and primary care setting in Sweden.

Thromb Res 2015 Aug 22;136(2):216-20. Epub 2015 Apr 22.

Department of Public Health and Clinical medicine, Umeå University, Sundsvall, Sweden.

Background: Warfarin treatment in Sweden holds a high standard with time in therapeutic range (TTR) over 75%. Internationally, specialized anticoagulation clinics (ACC) have shown higher TTR compared to primary health care centres (PHCC).

Objectives: To compare warfarin treatment quality in Sweden for ACC versus PHCC, thereby clarifying whether centralization is for the better.

Patients/methods: In total 77.058 patients corresponding to 217.058 treatment years with warfarin in the Swedish national quality register AuriculA from 1. Jan 2006 to 31. Dec 2011. Information regarding TTR was calculated from AuriculA, while patient characteristics and complications were retrieved from the Swedish National Patient Register.

Results: Of the 100.554 treatment periods examined, 78.7% were monitored at ACC. Mean TTR for INR 2-3 for all patients irrespective of intended target range was 76.5% with an annual risk of bleeding or thrombotic events of 2.24% and 2.66%, respectively. TTR was significantly higher in PHCC compared to ACC (79.6% vs. 75.7%, p<0.001), with no significant difference in overall risk of complications. Treatment periods for atrial fibrillation, except intended direct current conversion, showed similar results between ACC and PHCC without significant difference in annual risk of bleeding (2.50% vs. 2.51%) or thrombosis (3.09% vs. 3.16%). After propensity score matching there was still no significant difference in complication risk found.

Conclusions: Warfarin treatment quality is consistently high in both ACC and PHCC when monitored through AuriculA in Sweden, both measured as TTR and as risk of complications. In this setting, centralized warfarin monitoring is not likely to improve the results.
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http://dx.doi.org/10.1016/j.thromres.2015.04.016DOI Listing
August 2015

Organic matter chlorination rates in different boreal soils: the role of soil organic matter content.

Environ Sci Technol 2012 Feb 17;46(3):1504-10. Epub 2012 Jan 17.

Department of Thematic Studies, Water and Environmental Studies, Linköping University, 58183 Linköping, Sweden.

Transformation of chloride (Cl(-)) to organic chlorine (Cl(org)) occurs naturally in soil but it is poorly understood how and why transformation rates vary among environments. There are still few measurements of chlorination rates in soils, even though formation of Cl(org) has been known for two decades. In the present study, we compare organic matter (OM) chlorination rates, measured by (36)Cl tracer experiments, in soils from eleven different locations (coniferous forest soils, pasture soils and agricultural soils) and discuss how various environmental factors effect chlorination. Chlorination rates were highest in the forest soils and strong correlations were seen with environmental variables such as soil OM content and Cl(-) concentration. Data presented support the hypothesis that OM levels give the framework for the soil chlorine cycling and that chlorination in more organic soils over time leads to a larger Cl(org) pool and in turn to a high internal supply of Cl(-) upon dechlorination. This provides unexpected indications that pore water Cl(-) levels may be controlled by supply from dechlorination processes and can explain why soil Cl(-) locally can be more closely related to soil OM content and the amount organically bound chlorine than to Cl(-) deposition.
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http://dx.doi.org/10.1021/es203191rDOI Listing
February 2012

Temperature sensitivity indicates that chlorination of organic matter in forest soil is primarily biotic.

Environ Sci Technol 2009 May;43(10):3569-73

Department of Geology and Geochemistry, Stockholm University, SE-106 91 Stockholm, Sweden.

Old assumptions that chloride is inert and that most chlorinated organic matter in soils is anthropogenic have been challenged by findings of naturally formed organochlorines. Such natural chlorination has been recognized for several decades, but there are still very few measurements of chlorination rates or estimates of the quantitative importance of terrestrial chlorine transformations. While much is known about the formation of specific compounds, bulk chlorination remains poorly understood in terms of mechanisms and effects of environmental factors. We quantified bulk chlorination rates in coniferous forest soil using 36Cl-chloride in tracer experiments at different temperatures and with and without molecular oxygen (O2). Chlorination was enhanced by the presence of O2 and had a temperature optimum at 20 degrees C. Minimum rates were found at high temperatures (50 degrees C) or under anoxic conditions. The results indicate (1) that most of the chlorination between 4 and 40 degrees C was biotic and driven by O2 dependent enzymes, and (2) that there is also slower background chlorination occurring under anoxic conditions at 20 degrees C and under oxic conditions at 50 degrees C. Hence, while oxic and biotic chlorination clearly dominated, chlorination by other processes including possible abiotic reactions was also detected.
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http://dx.doi.org/10.1021/es8035779DOI Listing
May 2009

Chloride retention and release in a boreal forest soil: effects of soil water residence time and nitrogen and chloride loads.

Environ Sci Technol 2006 May;40(9):2977-82

Department of Geology and Geochemistry, Stockholm University, 106 91 Stockholm, Sweden.

The common assumption that chloride (Cl-) is conservative in soils and can be used as a groundwater tracer is currently being questioned, and an increasing number of studies indicate that Cl- can be retained in soils. We performed lysimeter experiments with soil from a coniferous forest in southeast Sweden to determine whether pore water residence time and nitrogen and Cl- loads affected Cl- retention. Over the first 42 days there was a net retention of Cl- with retention rates averaging 3.1 mg CI- m(-2) d(-1) (68% of the added Cl- retained over 42 days). Thereafter, a net release of Cl- at similar rates was observed for the remaining experimental period (85 d). Longer soil water residence time and higher Cl- load gave higher initial retention and subsequent release rates than shorter residence time and lower Cl- load did. Nitrogen load did not affect Cl transformation rates. This study indicates that simultaneous retention and release of Cl- can occur in soils, and that rates may be considerable relative to the load. The retention of Cl- observed was probably due to chlorination of soil organic matter or ion exchange. The cause of the shift between net retention and net release is unclear, but we hypothesize that the presence of O2 or the presence of microbially available organic matter regulates Cl- retention and release rates.
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http://dx.doi.org/10.1021/es0523237DOI Listing
May 2006

Multi-objective environmental management in constructed wetlands.

Environ Monit Assess 2004 Jan;90(1-3):171-85

Man-Technology-Environment Research Centre, Orebro University, Orebro, Sweden.

We examined multi-objective environmental management as applied to pursuing concurrent goals of water treatment, biodiversity and promotion of recreation in constructed wetlands. A case study of a wetland established to treat landfill leachate, increase biodiversity, and promote recreation was evaluated. The study showed that attempts to combine pollution management with activities promoting biodiversity or recreation are problematic in constructed wetlands. This could be because the typical single-objective focus of scientific research leads to contradictions when planning, implementing and assessing the multi-objective use of wetlands. In the specific case of wetland filters for landfill leachate treatment, biodiversity, and recreation, there is a need for further research that meet practical needs to secure positive outcomes.
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http://dx.doi.org/10.1023/b:emas.0000003577.22824.8eDOI Listing
January 2004

Spatial patterns of organic chlorine and chloride in Swedish forest soil.

Chemosphere 2003 Jul;52(2):391-7

Department of Thematic Studies, University of Linköping, SE-602 24 Norrköping, Sweden.

The concentration of organic carbon, organic chlorine and chloride was determined in Swedish forest soil in the southern part of Sweden and the spatial distribution of the variables were studied. The concentration of organically bound chlorine was positively correlated to the organic carbon content, which is in line with previous studies. However, the spatial distribution patterns strongly indicate that some other variable adds structure to the spatial distribution of organic chlorine. The distribution patterns for chloride strongly resembled the distribution of organic chlorine. The spatial distribution of chloride in soil depends on the deposition pattern which in turn depends on prevailing wind-direction, amount of precipitation and the distance from the sea. This suggests that the occurrence of organic chlorine in soil is influenced by the deposition of chloride or some variable that co-varies with chloride. Two clearly confined strata were found in the area: the concentrations of organic chlorine and chloride in the western area were significantly higher than in the eastern area. No such difference among the two areas was seen regarding the carbon content.
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http://dx.doi.org/10.1016/S0045-6535(03)00193-0DOI Listing
July 2003