| 1. |
- Mavaddat, Nasim, et al.
(författare)
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Prediction of Breast Cancer Risk Based on Profiling With Common Genetic Variants
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 107:5, s. 036-036
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Tidskriftsartikel (refereegranskat)abstract
- Background: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. Methods: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. Results: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. Conclusions: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.
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| 2. |
- Waldemar, Annette, et al.
(författare)
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In-hospital family-witnessed resuscitation with a focus on the prevalence, processes, and outcomes of resuscitation : A retrospective observational cohort study
- 2021
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Ingår i: Resuscitation. - : Elsevier. - 0300-9572 .- 1873-1570. ; 165:August, s. 23-30
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Tidskriftsartikel (refereegranskat)abstract
- Aim: International and national guidelines support in-hospital, family-witnessed resuscitation, provided that patients are not negatively affected. Empirical evidence regarding whether family presence interferes with resuscitation procedures is still scarce. The aim was to describe the prevalence and processes of family-witnessed resuscitation in hospitalised adult patients, and to investigate associations between family-witnessed resuscitation and the outcomes of resuscitation.Methods: Nationwide observational cohort study based on data from the Swedish Registry of Cardiopulmonary Resuscitation.Results: In all, 3257 patients with sudden, in-hospital cardiac arrests were included. Of those, 395 had family on site (12%), of whom 186 (6%) remained at the scene. It was more common to offer family the option to stay during resuscitation if the cardiac arrest occurred in emergency departments, intensive-care units or cardiac-care units, compared to hospital wards (44% vs. 26%, p < 0.001). It was also more common for a staff member to be assigned to take care of family in acute settings (68% vs. 56%, p = 0.017). Mean time from cardiac arrest to termination of resuscitation was longer in the presence of family (20.67 min vs. 17.49 min, p = 0.020), also when controlling for different patient and contextual covariates in a regression model (Stand (b) 0.039, p = 0.027). No differences were found between family-witnessed and non-family-witnessed resuscitation in survival immediately after resuscitation (57% vs. 53%, p = 0.291) or after 30 days (35% vs. 29%, p = 0.086).Conclusions: In-hospital, family-witnessed resuscitation is uncommon, but the processes and outcomes do not seem to be negatively affected, suggesting that staff should routinely invite family to witness resuscitation.
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| 3. |
- Agerström, Jens, et al.
(författare)
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All else equal : Examining treatment bias and stereotypes based on patient ethnicity and socioeconomic status using in-hospital cardiac arrest clinical vignettes
- 2024
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Ingår i: Heart and Lung. - : MOSBY-ELSEVIER. - 0147-9563 .- 1527-3288. ; 63, s. 86-91
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Tidskriftsartikel (refereegranskat)abstract
- Background: Research on ethnic and socioeconomic treatment differences following in-hospital cardiac arrest (IHCA) largely draws on register data. Due to the correlational nature of such data, it cannot be concluded whether detected differences reflect treatment bias/discrimination – whereby otherwise identical patients are treated differently solely due to sociodemographic factors. To be able to establish discrimination, experimental research is needed. Objective: The primary aim of this experimental study was to examine whether simulated IHCA patients receive different treatment recommendations based on ethnicity and socioeconomic status (SES), holding all other factors (e.g., health status) constant. Another aim was to examine health care professionals’ (HCP) stereotypical beliefs about these groups. Methods: HCP (N = 235) working in acute care made anonymous treatment recommendations while reading IHCA clinical vignettes wherein the patient's ethnicity (Swedish vs. Middle Eastern) and SES had been manipulated. Afterwards they estimated to what extent hospital staff associate these patient groups with certain traits (stereotypes). Results: No significant differences in treatment recommendations for Swedish versus Middle Eastern or high versus low SES patients were found. Reported stereotypes about Middle Eastern patients were uniformly negative. SES-related stereotypes, however, were mixed. High SES patients were believed to be more competent (e.g., respected), but less warm (e.g., friendly) than low SES patients. Conclusions: Swedish HCP do not seem to discriminate against patients with Middle Eastern or low SES backgrounds when recommending treatment for simulated IHCA cases, despite the existence of negative stereotypes about these groups. Implications for health care equality and quality are discussed.
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| 4. |
- Bennesved, Anna, et al.
(författare)
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Ambulance clinicians’ understanding of older patients’ self-determination : A vignette study
- 2023
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Ingår i: Nursing Ethics. - : Sage Publications. - 0969-7330 .- 1477-0989. ; , s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Older patients are often vulnerable and highly dependent on healthcare professionals’ assessment in the event of acute illness. In the context of ambulance services, this poses challenges as the assessment is normally conducted with a focus on identifying life-threatening conditions. Such assessment is not fully satisfactory in a patient relationship that also aims to promote and protect patient autonomy.Aim: To describe ambulance clinicians’ understanding of older patients’ self-determination when the pa- tient’s decision-making ability is impaired.Research design: A qualitative design with an inductive approach, guided by descriptive phenomenology.Participants: In total, 30 ambulance clinicians, comprised of 25 prehospital emergency nurses, 1 nurse and 4 emergency medical technicians participated in 15 dyadic interviews.Ethical considerations: The research was conducted in accordance with the Declaration of Helsinki, and permission was granted by the Swedish Ethical Review Authority.Findings: The findings are presented in two themes: (1) Movement between explicit and implicit will; and (2) Contradictions about the patient’s best interests. The clinicians’ interpretations are based on an understanding of the patient’s situation using substitute decision-making in emergency situations and conversations that reveal the patient’s explicit wishes. Sometimes the clinicians collaborate to validate the patient’s implicit will, while they at other times subordinate themselves to others’ opinions. The clinicians find themselves in conflict between personal values and organisational values as they try to protect the patient’s self-determination.Conclusion: The results indicate that older patients with an impaired decision-making ability risk losing the right to self-determination in the context of ambulance services. The clinicians face challenges that significantly affect their ability to handle the older patient’s unique needs based on a holistic perspective and their ability to be autonomous.
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| 5. |
- Berntsson, Tommy, et al.
(författare)
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Ambulanssjukvården måste bli jämlik
- 2013
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Ingår i: Helsingborgs Dagblad. - Helsingborg : Helsingborgs Dagblad. - 1103-9388. ; 2013-06-17
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Skiftande vårdkvalité hotar patientsäkerheten inom ambulanssjukvården. Nu måste regeringen och Socialstyrelsen skapa nationella riktlinjer, skriver Nätverket för utbildning av ambulanssjuksköterskor .
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| 6. |
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| 7. |
- Bremer, Anna, et al.
(författare)
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Copy number variation characteristics in subpopulations of patients with autism spectrum disorders.
- 2011
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Ingår i: American Journal of Medical Genetics, Part B, Neuropsychiatric Genetics. - : Wiley. - 1552-4841. ; 156B156:2, s. 115-124
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Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorders (ASDs) are a heterogeneous group of disorders with a complex genetic etiology. We used high-resolution whole genome array-based comparative genomic hybridization (array-CGH) to screen 223 ASD patients for gene dose alterations associated with susceptibility for autism. Clinically significant copy number variations (CNVs) were identified in 18 individuals (8%), of which 9 cases (4%) had de novo aberrations. In addition, 20 individuals (9%) were shown to have CNVs of unclear clinical relevance. Among these, 13 cases carried rare but inherited CNVs that may increase the risk for developing ASDs, while parental samples were unavailable in the remaining seven cases. Classification of all patients into different phenotypic and inheritance pattern groups indicated the presence of different CNV patterns in different patient groups. Clinically relevant CNVs were more common in syndromic cases compared to non-syndromic cases. Rare inherited CNVs were present in a higher proportion of ASD cases having first- or second-degree relatives with an ASD-related neuropsychiatric phenotype in comparison with cases without reported heredity (P=0.0096). We conclude that rare CNVs, encompassing potential candidate regions for ASDs, increase the susceptibility for the development of ASDs and related neuropsychiatric disorders giving us further insight into the complex genetics underlying ASDs
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| 8. |
- Bremer, Anna, et al.
(författare)
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Screening for Copy Number Alterations in Loci Associated With Autism Spectrum Disorders by Two-Color Multiplex Ligation-Dependent Probe Amplification
- 2010
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Ingår i: American journal of medical genetics. Part B, Neuropsychiatric genetics. - : Wiley. - 1552-4841 .- 1552-485X. ; 153B:1, s. 280-285
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Tidskriftsartikel (refereegranskat)abstract
- The autism spectrum disorder (ASD) is a heterogenous condition characterized by impaired socialization and communication in association with stereotypic behaviors. ASD is highly heritable and heterogeneous with a complex genetic etiology. Recurrent submicroscopic deletions or duplications have been identified in a subgroup of individuals with ASD using array technology. Adequate genetic testing for these genomic imbalances have not yet been widely implemented in the diagnostic setting due to lack of feasible and cost-effective methods as well as difficulties to interpret the clinical significance of these small copy number variants (CNVs). We developed a multiplex ligation-dependent probe amplification (MLPA) assay to investigate its usefulness for detection of copy number alterations (CNAs) in autistic patients. This test proved to be easy to perform, fast, cost-effective, and suitable for reliable detection of multiple loci in a single reaction. We screened 148 autistic patients for 15 different loci covering 26 genes and found a 15q11-13 interstitial duplication that had escaped detection by conventional karyotyping in 1.3% of the patients. Synthetic probe MLPA allows for a flexible analysis of a continuously increasing number of CNAs associated with autism. Our result show that MLPA assay is an easy and cost-effective method for the identification of selected CNAs in diagnostic laboratories. (C) 2009 Wiley-Liss, Inc.
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| 9. |
- Bremer, Anna
(författare)
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Unraveling genetic mechanisms in autism spectrum disorders
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Autism Spectrum Disorders (ASDs) are a group of neurodevelopmental disorders characterized by impairments in socialization and communication accompanied by repetitive and stereotypic behaviors. ASDs are highly heritable and heterogeneous with a complex genetic etiology. Numerous candidate genes have been suggested by linkage, association and candidate gene studies and recurrent submicroscopic deletions and duplications have been identified using array technology. In order to screen for deletions and duplications in ASD candidate genes and regions, we developed a Multiplex Ligation-dependent Probe Amplification (MLPA) assay (paper I). Screening of 26 genes in 148 individuals we found a 15q11-13 interstitial duplication, which had escaped detection by conventional karyotyping, in 1.3% of the patients. Synthetic MLPA showed to be an easy, reliable and cost-effective method for the identification of Copy Number Variants (CNVs) in selected candidate regions. In order to screen the whole genome for CNVs in ASD patients and identify alterations associated with susceptibility for ASDs we used high resolution array-based comparative genomic hybridization (array-CGH). In 4-year-old girl we identified a 7.1 Mb interstitial deletion of chromosome band 6p22.3 (paper II). The patient had cognitive delay, specific language impairments and dysmorphic features. The deletion overlapped with six previously reported cases with a 6p22–24 interstitial deletion. Developmental delay was present in all cases, while heart defects, short neck and/or redundant skin folds, eye abnormalities, and ear anomalies were present in the majority of cases. By our finding we could narrow down the critical region for the 6p22 deletion phenotype to 2.2 Mb comprising twelve genes including the ATXN1 gene previously reported susceptibility gene for learning difficulties. In the whole genome screening of 223 ASD patients by array-CGH (paper III), clinically significant CNVs were identified in 18 individuals (8%) and CNVs of unclear clinical relevance in 20 individuals (9%). Among the latter cases, 13 individuals carried rare inherited CNVs, while parental samples were unavailable in the remaining seven cases. All patients were classified into different phenotype and inheritance subgroups. Rare inherited CNVs were present in a higher proportion of ASD cases having first- or second-degree relatives with an ASD related neuropsychiatric phenotype in comparison with cases without reported heredity (P=0.0096). We concluded that rare CNVs, encompassing potential candidate regions for ASDs, increase the susceptibility for ASDs and related neuropsychiatric disorders. In 514 ASD patients screened by array-CGH (paper IV), an exonic PARK2 deletion was found in three cases (~0.6%). No such deletion was identified in 149 control subjects. In a summary of comparable CNVs reported in the Database of Genomic Variants (DGV), 9/5141 controls had a deletion within the PARK2 gene (~0.2%). Compared with the DGV controls, deletions in the PARK2 gene were significantly more common in our ASD patient cohort (p=0.019). PARK2 deletions have previously been reported in autism and our results further support that PARK2 deletions may be a risk factor for the development of ASDs. PARK2 encodes for the E3 ubiquitin-protein ligase Parkin, which belongs to the Ubiquitin proteasome system (UPS). UPS operate pre- and postsynaptic compartments demonstrating a direct link between these two major systems that may be important in the pathophysiology of autism. The future challenge will be to, in combination with the increased usage of high resolution array-CGH and whole genome sequencing identifying genetic alterations, create useful analysis systems in which the co-occurring pathways and gene-gene interactions in ASDs can be linked together and the different genes involved identified.
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| 10. |
- Bremer, Anders, 1957-
(författare)
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Vid existensens gräns : Etiskt vårdande och professionellt ansvar vid hjärtstopp utanför sjukhus
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aim: To describe and interpret patients’, family members’ and ambulance personnel’s experiences with regard to survival, attendance, and caring at cardiac arrests and deaths, and to analyze ethical conflicts that arise in relation to families and how the personnel’s ethical competence can affect caring and the ability to handle ethical problems.Method: The three interview studies were guided by a reflective lifeworld approach grounded in phenomenology and analyzed by searching for the essence of the phenomenon in two studies and by attaining a main interpretation in one study. In the fourth study, the general approach was supplemented by “reflective equilibrium” that guided the ethical analysis.Results: The survivors are striving towards a good life by means of efforts to reach meaning and coherence, facing existential fear and insecurity as well as gratitude and the joy of life. Family members lose everyday control through feelings of unreality, inadequacy and overwhelming responsibility. Ambulance personnel’s care mediates hope and despair until the announcement of survival or death. After the event, family members risk involuntary loneliness and anxiety about the future. For the ambulance personnel, caring for families involves a need for mobility in decision making, forcing the personnel to balance their own perceptions, feelings and reactions against interpretative reasoning. To base decision making on emotional reactions creates the risk of erroneous conclusions and a care relationship with elements of dishonesty, misdirected benevolence and false hopes. Identification with family members can promote recognition of and response to their existential needs, but also frustrate meeting family members emotions’ and handling one’s own vulnerability and inadequacy. It was found that futile cardiopulmonary resuscitation, administered to patients for the benefit of family members, is not an acceptable moral practice, due both to norms of not deliberately treating persons as mere means and to norms of taking care of families.Conclusions: Ethical conflicts exist when it comes to conveying realistic hope, relief from guilt, participation, responsibility for decision making, and fairness in the professional role. Ambulance personnel need support to enhance ethical caring competence and to deal with personal discomfort, as well as clear guidelines on family support.
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