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21.
  • Andersson, Lisa, et al. (författare)
  • Investigating opioid-related fatalities in southern Sweden : contact with care-providing authorities and comparison of substances
  • 2020
  • Ingår i: Harm Reduction Journal. - : Springer Science and Business Media LLC. - 1477-7517. ; 17:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Opioid-related deaths have increased in Western countries over recent decades. Despite numerous studies investigating opioid-related mortality, only a few have focused on the lives of the deceased individuals prior to their deaths, specifically regarding contact with care-providing authorities such as health, social and correctional services. Furthermore, a change has been noted in the last two decades as to which opioids cause most deaths, from heroin to prescription opioids. However, studies comparing fatalities caused by different substances are rare. The aim of this study was to investigate contact with care-providing authorities during the year prior to death among individuals who died as a result of opioid intoxication and to analyse differences relating to which opioids caused their deaths. METHODS: The study is based on retrospective register data and includes 180 individuals with a history of illicit drug use, who died from opioid intoxication in Skåne, Sweden, between 1 January 2012 to 31 December 2013 and 1 July 2014 to 30 June 2016. Intoxications caused by heroin, methadone, buprenorphine and fentanyl were included. Data were collected from the National Board of Forensic Medicine, regional health care services, municipal social services and the Prison and Probation Service. Statistical testing was performed using Pearson's chi-square test, Fisher's exact test and the Mann-Whitney U test to analyse group differences. RESULTS: A total of 89% of the deceased individuals had been in contact with one or more of the care-providing authorities during the year prior to death; 75% had been in contact with health care, 69% with the social services, 28% with the Prison and Probation Service, and 23% had been enrolled in opioid substitution treatment at some point during their final year of life. Few differences appeared between the substance groups with regard to which opioid contributed to the death. In addition to opioids, sedatives were present in more than 80% of the cases. Individuals whose deaths were buprenorphine-related had been in contact with the social services to a significantly lesser extent during the year prior to death. CONCLUSIONS: The studied population is characterised by extensive contact with care-providing authorities, thus providing numerous opportunities for authorities to reach this group with preventive and other interventions. Few differences emerged between groups with regard to which opioid had contributed to the death.
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22.
  • Andersson, Lisa, et al. (författare)
  • Patient choice as a means of empowerment in opioid substitution treatment : a case from Sweden
  • 2020
  • Ingår i: Drugs. - : Taylor & Francis. - 0968-7637 .- 1465-3370. ; 27:2, s. 105-117
  • Tidskriftsartikel (refereegranskat)abstract
    • Patient choice of treatment provider was introduced within opioid substitution treatment in the southern Swedish county of Skåne in 2014. Substitution treatment has often been criticised for being strict, rule-based, and driven by an ethos of discipline. This study explores the patients’ views and experiences of patient choice, particularly as a potential means of empowerment. The study is based on semi-structured interviews with 33 patients at six substitution treatment clinics in two cities. Patient choice within substitution treatment has empowered the patients in that many are able to choose their treatment provider and transfer to another provider. The interviewees appreciated the possibility to choose and transfer, and felt that they had gained more influence on their treatment. Experiences of poor staff conduct and the new clinic’s policies and practice on prescribing benzodiazepines were important reasons for choosing and transferring between clinics. In particular, the patients stressed the importance of the possibility to leave a clinic they felt offered substandard treatment, and the psychologically important feeling of knowing that they could transfer to another facility. However, patient choice in addiction treatment is very rare in Sweden, and the demographic structure limits the development of patient choice within substitution treatment.
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23.
  • Andersson, Lisa (författare)
  • Problematisk opioidanvändning : om opioidrelaterade dödsfall och LARO i södra Sverige
  • 2021
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Problematic opioid use constitutes an extensive global problem. Correspondingly, opioid-related mortality is high and has increased in several Western countries, including Sweden, during the 2000s. In Sweden, the most effective treatment method, opioid substitution treatment (OST), was for a long time limited with respect to the number of patients. The treatment was also characterized by strict rules and conducted in a high-threshold manner, which has meant that it has not been fully appealing to people with problematic opioid use. Therefore, in Skåne County in southern Sweden, patient choice of treatment provider was introduced for OST in 2014 with the intention to increase the number of treatment places and strengthen patient empowerment. The overall aims of this thesis are (1) to investigate opioid-related deaths in Skåne with a focus on contact with care-providing authorities and in relation to increased access to OST, and (2) to examine patients’ and clinic managers’ attitudes towards the introduction of the patient choice reform for OST and their views of the reform's objectives of increased accessibility to OST and strengthening patients' empowerment and influence over their treatment.The four papers in this thesis are based on two research projects with various empiric material. Paper I and II are based on data on opioid overdose deaths from a period of two years before and two years following the introduction of the patient choice reform. Forensic data regarding the presence of various substances and which opioid caused the death, as well as demographic data and information on contact with care-providing authorities (health care, social services, and the Prison and Probation Service), were collected. Paper I examines clinical background and contact with care-providing authorities of opioid-related fatalities, as well as differences with regard to which opioid caused the death. Paper II examines the possible impact of the intervention on the development of opioid-related deaths in the region. National mortality data were also used in this study to investigate the development in Skåne compared to the rest of Sweden. The second research project focused on stakeholders’ views on the implementation of the patient choice reform. Paper III includes interviews with 33 OST patients, and paper IV consists of interviews with the managers of all OST clinics in Skåne. The results from paper I show that of the 180 deceased in opioid overdose included in the study, almost 90 per cent had been in contact with one of the examined care-providing authorities during the year prior to death. Few differences appeared with regard to which opioid contributed to the death. Paper II indicates that there has been no significant change in opioid-related deaths in Skåne after the patient choice reform and increased access to OST. An analysis on national mortality data however showed a significant yearly decrease in drug-related deaths in Skåne compared to other Swedish counties in the years following the reform (2015–2017). No change was noted in deaths related to methadone or buprenorphine in Skåne. The proportion of deaths among patients in OST increased after the introduction of the reform. The third paper indicates that patients in OST in Skåne have gained increased empowerment and influence over their treatment since the patient choice reform was introduced. Patients especially appreciated the knowledge that they could make an exit and change clinics if they so wished, even if they so far had chosen not to. In paper IV, the clinic managers were largely positive to the trend towards increased influence for patients over their treatment situation. They were more critical of the fact that there was no major differentiation between treatment providers, and that the competition that arose after the patient choice reform mainly was related to prescribing benzodiazepines.Conclusions drawn from the papers in this thesis include that patient choice of treatment provider can be viewed as a means of empowerment for patients in OST, which was regarded as positive by both patients and treatment providers. The limitations of such a system for providing OST that emerged were lack of diversity between clinics and that the competition between treatment providers largely comprised of differing views on the prescription of benzodiazepines. Further, improved access to low-threshold OST in Skåne was not associated with an increased overdose death-rate. The result that people who died from opioid overdose to a very large extent are known to society’s care-providing authorities suggests that there are considerable opportunities to reach people with problematic opioid use for therapeutic and harm reducing measures such as low-threshold OST and take-home naloxone.
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26.
  • Berman, Sara E, et al. (författare)
  • Intracranial Arterial 4D-Flow is Associated with Metrics of Brain Health and Alzheimer's Disease.
  • 2015
  • Ingår i: Alzheimer's & dementia (Amsterdam, Netherlands). - : Wiley. - 2352-8729. ; 1:4, s. 420-428
  • Tidskriftsartikel (refereegranskat)abstract
    • While cerebrovascular disease has long been known to co-occur with Alzheimer's disease (AD), recent studies suggest an etiologic contribution to AD pathogenesis. We used 4D-Flow magnetic resonance imaging (MRI) to evaluate blood flow and pulsatility indices in the Circle of Willis. We hypothesized decreased mean blood flow and increased pulsatility, metrics indicative of poor vascular health, would be associated with cerebral atrophy and an AD cerebrospinal fluid (CSF) profile.
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27.
  • Biró, Péter, et al. (författare)
  • Modelling and optimisation in European Kidney Exchange Programmes
  • 2021
  • Ingår i: European Journal of Operational Research. - : Elsevier BV. - 0377-2217. ; 291:2, s. 447-456
  • Tidskriftsartikel (refereegranskat)abstract
    • The complex multi-criteria optimisation problems arising in Kidney Exchange Programmes have received considerable attention both in practice and in the scientific literature. Whereas theoretical advancements are well reviewed and synthesised, this is not the case for practice. We present a synthesis of models and methods applied in present European Kidney Exchange Programmes, which is based on detailed descriptions we created for this purpose. Most descriptions address national programmes, yet we also present findings on emerging cross-national programmes. The synthesis provides a systematic and detailed description of the models and methods the programmes use, revealing important commonalities as well as considerable variation among them. Rather than distilling a single best practice from these results, we find that the variation in models and methods arises because of variation in country characteristics, policies, and ethics. The synthesised state of the art may benefit future national and cross-national initiatives and direct future theoretical contributions within and across the boundaries of the Operations Research discipline.
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28.
  • Chami, Nathalie, et al. (författare)
  • Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits
  • 2016
  • Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 99:1, s. 8-21
  • Tidskriftsartikel (refereegranskat)abstract
    • Red blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an exome array. After conditional analyses and replication in 27,480 independent individuals, we identified 16 new RBC variants. We found low-frequency missense variants in MAP1A (rs55707100, minor allele frequency [MAF] = 3.3%, p = 2 x 10(-10) for hemoglobin [HGB]) and HNF4A (rs1800961, MAF = 2.4%, p < 3 x 10(-8) for hematocrit [HCT] and HGB). In African Americans, we identified a nonsense variant in CD36 associated with higher RBC distribution width (rs3211938, MAF = 8.7%, p = 7 x 10(-11)) and showed that it is associated with lower CD36 expression and strong allelic imbalance in ex vivo differentiated human erythroblasts. We also identified a rare missense variant in ALAS2 (rs201062903, MAF = 0.2%) associated with lower mean corpuscular volume and mean corpuscular hemoglobin (p < 8 x 10(-9)). Mendelian mutations in ALAS2 are a cause of sideroblastic anemia and erythropoietic protoporphyria. Gene-based testing highlighted three rare missense variants in PKLR, a gene mutated in Mendelian non-spherocytic hemolytic anemia, associated with HGB and HCT (SKAT p < 8 x 10(-7)). These rare, low-frequency, and common RBC variants showed pleiotropy, being also associated with platelet, white blood cell, and lipid traits. Our association results and functional annotation suggest the involvement of new genes in human erythropoiesis. We also confirm that rare and low-frequency variants play a role in the architecture of complex human traits, although their phenotypic effect is generally smaller than originally anticipated.
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29.
  • Craddock, Nick, et al. (författare)
  • Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
  • 2010
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
  • Tidskriftsartikel (refereegranskat)abstract
    • Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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30.
  • Deming, Yuetiva, et al. (författare)
  • Sex-specific genetic predictors of Alzheimer’s disease biomarkers
  • 2018
  • Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 136:6, s. 857-872
  • Tidskriftsartikel (refereegranskat)abstract
    • Cerebrospinal fluid (CSF) levels of amyloid-β 42 (Aβ42) and tau have been evaluated as endophenotypes in Alzheimer’s disease (AD) genetic studies. Although there are sex differences in AD risk, sex differences have not been evaluated in genetic studies of AD endophenotypes. We performed sex-stratified and sex interaction genetic analyses of CSF biomarkers to identify sex-specific associations. Data came from a previous genome-wide association study (GWAS) of CSF Aβ42 and tau (1527 males, 1509 females). We evaluated sex interactions at previous loci, performed sex-stratified GWAS to identify sex-specific associations, and evaluated sex interactions at sex-specific GWAS loci. We then evaluated sex-specific associations between prefrontal cortex (PFC) gene expression at relevant loci and autopsy measures of plaques and tangles using data from the Religious Orders Study and Rush Memory and Aging Project. In Aβ42, we observed sex interactions at one previous and one novel locus: rs316341 within SERPINB1 (p = 0.04) and rs13115400 near LINC00290 (p = 0.002). These loci showed stronger associations among females (β = − 0.03, p = 4.25 × 10−8; β = 0.03, p = 3.97 × 10−8) than males (β = − 0.02, p = 0.009; β = 0.01, p = 0.20). Higher levels of expression of SERPINB1, SERPINB6, and SERPINB9 in PFC was associated with higher levels of amyloidosis among females (corrected p values < 0.02) but not males (p > 0.38). In total tau, we observed a sex interaction at a previous locus, rs1393060 proximal to GMNC (p = 0.004), driven by a stronger association among females (β = 0.05, p = 4.57 × 10−10) compared to males (β = 0.02, p = 0.03). There was also a sex-specific association between rs1393060 and tangle density at autopsy (pfemale = 0.047; pmale = 0.96), and higher levels of expression of two genes within this locus were associated with lower tangle density among females (OSTN p = 0.006; CLDN16 p = 0.002) but not males (p ≥ 0.32). Results suggest a female-specific role for SERPINB1 in amyloidosis and for OSTN and CLDN16 in tau pathology. Sex-specific genetic analyses may improve understanding of AD’s genetic architecture.
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