| 1. |
- Duc, Duong, 1984-
(författare)
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Healthcare context for knowledge translation in Vietnam : Development and application of the Context Assessment for Community Health (COACH) tool
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The failure to translate evidence into clinical practice has been repeatedly highlighted. This failure is partly attributed to disregarding the context within which healthcare is delivered. The aim of this thesis was to develop and psychometrically evaluate the Context Assessment for Community Health (COACH) tool, and, through that process, provide opportunities to measure aspects of context perceived to be important for Knowledge Translation (KT) interventions in low- and middle-income countries (LMIC).All four studies in this thesis were mainly undertaken in Quang Ninh province, Vietnam during 2008–2014. Study II, however, was also conducted in four other LMICs (Bangladesh, Nicaragua, South Africa, and Uganda). Study I employed inductive content analysis of 16 focus group discussions to explore the influence of context in a community-based facilitation intervention in Vietnam. Studies II and III reported on the development of the COACH tool and assessment of its psychometric properties. Study IV used the COACH tool in a survey among health workers in Vietnam.To date, three sources of evidence regarding validity of the COACH tool have been provided, that is, test content, response processes, and internal instrument structure, with promising psychometric characteristics. The COACH tool could be used as means of characterizing aspects of context ahead of KT interventions, for tailoring KT strategies, and for further understanding of the results of KT interventions.
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| 2. |
- Grut, Viktor, et al.
(författare)
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Cytomegalovirus seropositivity is associated with reduced risk of multiple sclerosis : a presymptomatic case-control study
- 2021
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Ingår i: European Journal of Neurology. - : Blackwell Publishing. - 1351-5101 .- 1468-1331. ; 28:9, s. 3072-3079
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Epstein-Barr virus (EBV) and Human herpesvirus 6A (HHV-6A) are associated with increased risk of multiple sclerosis (MS). Conversely, infection with Cytomegalovirus (CMV) has been suggested to reduce the risk of MS but supporting data from presymptomatic studies are lacking. Here, we sought to increase the understanding of CMV in MS aetiology.METHODS: We performed a nested case-control study with presymptomatically collected blood samples identified through cross-linkage of MS registries and Swedish biobanks. Serological antibody response against CMV, EBV and HHV-6A was determined using a bead-based multiplex assay. Odds ratio (OR) with 95 % confidence intervals (CI) for CMV seropositivity as risk factor for MS was calculated by conditional logistic regression and adjusted for EBV and HHV-6A seropositivity. Potential interactions on the additive scale were analysed by calculating attributable proportion due to interaction (AP).RESULTS: Serum samples from 670 pairs of matched cases and controls were included. CMV seropositivity was associated with a reduced risk for MS (OR = 0.70, 95% CI 0.56-0.88, p = 0.003). Statistical interactions on the additive scale were observed between seronegativity for CMV and seropositivity against HHV-6A (AP 0.34, 95% CI 0.06-0.61) and EBV antigen EBNA-1 (amino acid 385-420) at age 20-39 years (AP 0.37, 95% CI 0.09-0.65).CONCLUSIONS: CMV seropositivity is associated with a decreased risk for MS. The protective role for CMV infection in MS aetiology is further supported by the interactions between CMV seronegativity and EBV and HHV-6A seropositivity.
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| 3. |
- Grut, Viktor, et al.
(författare)
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Human herpesvirus 6A and axonal injury before the clinical onset of multiple sclerosis
- 2024
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Ingår i: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 147:1, s. 177-185
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Tidskriftsartikel (refereegranskat)abstract
- Recent research indicates that multiple sclerosis is preceded by a prodromal phase with elevated levels of serum neurofilament light chain (sNfL), a marker of axonal injury. The effect of environmental risk factors on the extent of axonal injury during this prodrome is unknown. Human herpesvirus 6A (HHV-6A) is associated with an increased risk of developing multiple sclerosis. The objective of this study was to determine if HHV-6A serostatus is associated with the level of sNfL in the multiple sclerosis prodrome, which would support a causative role of HHV-6A.A nested case-control study was performed by crosslinking multiple sclerosis registries with Swedish biobanks. Individuals with biobank samples collected before the clinical onset of multiple sclerosis were included as cases. Controls without multiple sclerosis were randomly selected, matched for biobank, sex, sampling date and age. Serostatus of HHV-6A and Epstein-Barr virus was analysed with a bead-based multiplex assay. The concentration of sNfL was analysed with single molecule array technology. The association between HHV-6A serology and sNfL was assessed by stratified t-tests and linear regressions, adjusted for Epstein-Barr virus serostatus and sampling age. Within-pair ratios of HHV-6A seroreactivity and sNfL were calculated for each case and its matched control. To assess the temporal relationship between HHV-6A antibodies and sNfL, these ratios were plotted against the time to the clinical onset of multiple sclerosis and compared using locally estimated scatterplot smoothing regressions with 95% confidence intervals (CI).Samples from 519 matched case-control pairs were included. In cases, seropositivity of HHV-6A was significantly associated with the level of sNfL (+11%, 95% CI 0.2-24%, P = 0.045) and most pronounced in the younger half of the cases (+24%, 95% CI 6-45%, P = 0.007). No such associations were observed among the controls. Increasing seroreactivity against HHV-6A was detectable before the rise of sNfL (significant within-pair ratios from 13.6 years versus 6.6 years before the clinical onset of multiple sclerosis).In this study, we describe the association between HHV-6A antibodies and the degree of axonal injury in the multiple sclerosis prodrome. The findings indicate that elevated HHV-6A antibodies both precede and are associated with a higher degree of axonal injury, supporting the hypothesis that HHV-6A infection may contribute to multiple sclerosis development in a proportion of cases.
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| 4. |
- Wetterbom, Anna, 1977-
(författare)
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Genome and Transcriptome Comparisons between Human and Chimpanzee
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The chimpanzee is humankind’s closest living relative and the two species diverged ~6 million years ago. Comparative studies of the human and chimpanzee genomes and transcriptomes are of great interest to understand the molecular mechanisms of speciation and the development of species-specific traits. The aim of this thesis is to characterize differences between the two species with regard to their genome sequences and the resulting transcript profiles. The first two papers focus on indel divergence and in particular, indels causing premature termination codons (PTCs) in 8% of the chimpanzee genes. The density of PTC genes is correlated with both the distance to the telomere and the indel divergence. Many PTC genes have several associated transcripts and since not all are affected by the PTC we propose that PTCs may affect the pattern of expressed isoforms. In the third paper, we investigate the transcriptome divergence in cerebellum, heart and liver, using high-density exon arrays. The results show that gene expression differs more between tissues than between species. Approximately 15% of the genes are differentially expressed between species, and half of the genes show different splicing patterns. We identify 28 cassette exons which are only included in one of the species, often in a tissue-specific manner. In the fourth paper, we use massive parallel sequencing to study the chimpanzee transcriptome in frontal cortex and liver. We estimate gene expression and search for novel transcribed regions (TRs). The majority of TRs are located close to genes and possibly extend the annotations. A subset of TRs are not found in the human genome. The brain transcriptome differs substantially from that of the liver and we identify a subset of genes enriched with TRs in frontal cortex. In conclusion, this thesis provides evidence of extensive genomic and transcriptomic variability between human and chimpanzee. The findings provide a basis for further studies of the underlying differences affecting phenotypic divergence between human and chimpanzee.
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| 5. |
- Brunell, Olivia
(författare)
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Improving neonatal health care in Nepal
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Every year, millions of newborns die globally due to poor quality of care around the time of birth. The overall aim of this thesis was to inform and test design of quality improvement (QI) interventions in Nepal. Contextual factors of importance for implementation of evidence-based newborn care practices were investigated, and the effect of a package of QI interventions on provision and experience of care was evaluated. In Paper I, we used focus group discussions and key informant interviews with delivery care staff to identify barriers and enablers for delayed umbilical cord clamping (DCC). Results indicate that delivery care staff needed knowledge of the benefits of DCC to gain motivation for change. Training, supervision and evaluation were requested to be able to change old routines, and they wanted authorized guidelines to bring uniformity in clinical practice. In Paper II, individual interviews with staff working with newborn infants were used to explore factors affecting parent-infant closeness in hospitals. Informants thought that offering a comfortable environment, privacy and counselling would enhance parent-infant closeness, but hospital resources were insufficient to achieve this. They described routines in the hospitals, and traditions and cultural beliefs in the society, which separated parents and newborns. In Paper III, a stepped-wedge randomized control design was applied to evaluate the effect of a QI package including training, facilitation and feedback, on patient satisfaction. The likelihood of women being overall satisfied with care during childbirth increased (aOR 1.66 [CI: 1.59-1.73, ICC: 0.275]) but the overall proportion of satisfaction was low, increasing from 58% to 62%. In Paper IV, clinical observations of early essential newborn care (EENC) practices were done before and after the introduction of the QI package. Overall, the rate of initiation of breastfeeding within one hour increased from 5% to 12%, and DCC increased from 22% to 33%. In conclusion, when designing interventions to improve quality of care, in Nepal or similar settings, it is important to use authorized guidelines and include education, training, supervision and evaluation. Hospital resources, routines and cultural beliefs need to be considered. The results indicate that a multi-pronged QI package can improve quality of newborn care in Nepal.
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| 6. |
- Kåks, Per, 1991-
(författare)
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Contextualising a South African social innovation for maternal and child health to mothers with experiences of migration in Sweden
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Despite a universally accessible and high-quality welfare system, disparities in health and wellbeing persist between families who have migrated to Sweden and the native population. The South African Mentor Mother programme, a social innovation for maternal and child health among socially disadvantaged communities, was transferred and adapted to benefit mothers and pregnant women with experiences of migrating to Sweden.This thesis aims to explore the adaptation, implementation and further development of the South African Mentor Mother programme in two locations in Sweden, based on professional and lived experience among various groups of stakeholders.In Study I, three workshops and eleven interviews were held with stakeholders to explore central aspects of the adaptation process. These aspects entailed prioritising social determinants of health over health behaviour change, using indirect mechanisms and social ripples to achieve change, prioritising referring clients over intervening directly, recruiting peer supporters with competencies responding to a heterogeneous socio-cultural context, and allowing flexibility in programme content and methods.In Study II, nineteen interviews with different stakeholders and digital field logs of peer support meetings (n=1,294) were used to evaluate the implementations of the programme. Contextual factors of importance included institutional mistrust, gender norms, unpredictable funding, and the organisation's third sector affiliation. Peer supporters prioritised linking clients to welfare services over educational intervention components, and sometimes experienced blurring between professional and personal roles. Practical support and trustful relationships emerged as important entry points to support more sensitive issues. In Study III, the photovoice method was used to conduct a focus group discussion and six interviews with Mentor Mothers and their coordinator in Gothenburg, exploring how they developed empowerment strategies perceived to be relevant, feasible and effective. These strategies consisted of various aspects of using both informative, practical, psychosocial and motivational support to meet community health and social needs.In Study IV, twenty-one interviews with Mentor Mothers, client mothers and other stakeholders were conducted to explore the emergence and management of mistrust in welfare services in Gothenburg. Mistrust was described to arise through rumours, unclear interactions with services, and lack of familiarity with the welfare system. Mentor Mothers used various strategies to build trusting relations with clients, which enabled them to promote institutional trust through information and humanisation of service providers.This thesis illustrates how innovative community-based solutions to complex societal problems can be transferred between contexts, implemented and further developed to ensure their relevance to the target group.
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| 7. |
- Medvedeva, Anna, 1981-
(författare)
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Performance of advanced tool steels for cutting tool bodies
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Performance of indexable insert cutting tools is not only about the performance of cutting inserts. It is also about the cutting tool body, which has to provide a secure and accurate insert positioning as well as its quick and easy handling under severe working conditions. The common damage mechanisms of cutting tool bodies are fatigue and plastic deformation. Cutting tools undergo high dynamic stresses going in and out cutting engagement; as a result, an adequate level of fatigue strength is the essential steel property. Working temperatures of tool bodies in the insert pocket can reach up to 600°C, why the tool steel requires high softening resistance to avoid plastic deformation. Machinability is also essential, as machining of the steel represents a large fraction of the production cost of a cutting tool. The overall aim of the study is to improve the tool body performance by use of an advanced steel grade with an optimized combination of all the demanding properties. Due to the high-temperature conditions, the thesis concerns mostly hot-work tool steels increasing also the general knowledge of their microstructure, mechanical properties and machinability. Knowing the positive effect of sulphur on machinability of steels, the first step was to indentify a certain limit of the sulphur addition, which would not reduce the fatigue strength of the tool body below an acceptable level. In tool bodies, where the demand on surface roughness was low and a geometrical stress concentrator was present, the addition of sulphur could be up to 0.09 wt%. Fatigue performance of the cutting tools to a large extent depended on the steel resistance to stress relaxation under high dynamic loading and elevated temperatures. The stress relaxation behaviour, material substructure and dislocation characteristics in low-alloyed and hot-work tool steels were studied using X-ray diffraction under thermal and mechanical loading. Different tool steels exhibited different stress relaxation resistance depending on their microstructure, temper resistance and working temperature. Hot-work tool steels showed to be more preferable to low-alloyed tool steels because of their ability to inhibit the rearrangement and annihilation of induced dislocations. High-temperature softening resistance of the hot-work tool steels was investigated during high-temperature hold-times and isothermal fatigue and discussed with respect to their microstructure. Carbide morphology and precipitation were determined using scanning and transmission electron microscopy. Machinability of a prehardened hot-work tool steel of varying nickel content from 1 to 5 wt% was investigated in end milling and drilling operations. Machining the higher nickel containing steels resulted in longer tool life and generated lower cutting forces and tool/workpiece interface temperature. The difference in machinability of the steels was discussed in terms of their microstructure and mechanical properties.
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| 8. |
- Sayols-Baixeras, Sergi, et al.
(författare)
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Streptococcus Species Abundance in the Gut Is Linked to Subclinical Coronary Atherosclerosis in 8973 Participants From the SCAPIS Cohort
- 2023
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Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 148:6, s. 459-472
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gut microbiota have been implicated in atherosclerotic disease, but their relation with subclinical coronary atherosclerosis is unclear. This study aimed to identify associations between the gut microbiome and computed tomography-based measures of coronary atherosclerosis and to explore relevant clinical correlates.Methods: We conducted a cross-sectional study of 8973 participants (50 to 65 years of age) without overt atherosclerotic disease from the population-based SCAPIS (Swedish Cardiopulmonary Bioimage Study). Coronary atherosclerosis was measured using coronary artery calcium score and coronary computed tomography angiography. Gut microbiota species abundance and functional potential were assessed with shotgun metagenomics sequencing of stool, and associations with coronary atherosclerosis were evaluated with multivariable regression models adjusted for cardiovascular risk factors. Associated species were evaluated for association with inflammatory markers, metabolites, and corresponding species in saliva.Results: The mean age of the study sample was 57.4 years, and 53.7% were female. Coronary artery calcification was detected in 40.3%, and 5.4% had at least 1 stenosis with >50% occlusion. Sixty-four species were associated with coronary artery calcium score independent of cardiovascular risk factors, with the strongest associations observed for Streptococcus anginosus and Streptococcus oralis subsp oralis (P<1×10-5). Associations were largely similar across coronary computed tomography angiography-based measurements. Out of the 64 species, 19 species, including streptococci and other species commonly found in the oral cavity, were associated with high-sensitivity C-reactive protein plasma concentrations, and 16 with neutrophil counts. Gut microbial species that are commonly found in the oral cavity were negatively associated with plasma indole propionate and positively associated with plasma secondary bile acids and imidazole propionate. Five species, including 3 streptococci, correlated with the same species in saliva and were associated with worse dental health in the Malmö Offspring Dental Study. Microbial functional potential of dissimilatory nitrate reduction, anaerobic fatty acid β-oxidation, and amino acid degradation were associated with coronary artery calcium score.Conclusions: This study provides evidence of an association of a gut microbiota composition characterized by increased abundance of Streptococcus spp and other species commonly found in the oral cavity with coronary atherosclerosis and systemic inflammation markers. Further longitudinal and experimental studies are warranted to explore the potential implications of a bacterial component in atherogenesis.
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| 9. |
- Unneby, Anna, 1985-
(författare)
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Pain and pain management with femoral nerve block following hip fracture : effects and experiences: the perspective of older patients and staff
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Older people with hip fractures are often frail with several comorbidities and roughly half of them have dementia disorders. Pain is common among patients with hip fracture and pain management in these patients is a challenge. Opioids are known to relieve pain while at rest but are not as effective in movement. One alternative to opioids is a femoral nerve block (FNB). Previous studies have shown that FNBs can decrease pain and the need for opioids, but these studies excluded patients with dementia. Few studies have investigated whether FNBs decrease the incidence of complications in general, and delirium in particular. These studies were also based on different types of nerve blocks and methods. Few studies have described patients’ experiences of pain and pain management, and there are no studies on patients’ experiences of receiving or being treated with FNBs. In addition, there are no studies on staff´s experience of nursing care among patients with hip fractures who received an FNB. Objectives: The overall aim of this thesis is to investigate the effect of a preoperative FNB in patients with hip fracture in terms of pain and complications, and, further, to describe experiences of pain and pain management among patients with hip fracture who received FNBs as well as staff´s experiences of treating them. The first two papers (I and II) investigate the effect of an FNB compared to opioids, with a focus on pain and complications. To gain a deeper understanding, the final two papers (III and IV) describe experiences of pain and pain management in patients with hip fractures who received an FNB, and the staff's experiences of nursing care with patients with hip fractures who received an FNB. Methods: Papers I and II are based on a randomized controlled study which included patients aged 70 years or older with hip fractures, including those with cognitive impairment or dementia. Patients were randomized on arrival at the orthopaedic ward in terms of pain treatment to be administered; the options were FNB (with opioids if needed) or opioids alone. In paper I, 266 patients were included; the mean age was 84 years, 64% were women, and 45% had a dementia diagnosis. Paper II included 236 patients; the mean age was the same, 66% were women, and 46% had a dementia diagnosis. Pain assessment scales (self-rated VAS and VAS by proxy) was used preoperative to assess patients’ pain in rest. Nurses assessed the incidence of delirium using Nu-DESC, both pre- and postoperatively. In addition, a structural interview was performed with validated assessments 3 to 5 days after surgery by the author (AU). The assessments, nursing and medical records were subsequently evaluated by a specialist in geriatric medicine together with a trained research nurse in terms of complications, dementia, depression and delirium. Data collected in papers I and II were analysed using comparative and descriptive statistical analysis. In papers III and IV, semi-structured interviews were performed with patients (paper III) and with staff (nurses and assistant nurses, paper IV) based on interview guides with open-ended questions that offered opportunities for clarification and follow-up questions. In paper III, 23 patients with hip fractures aged 70 years or older who were treated with FNBs were interviewed, and in paper IV, staff working in the orthopaedic ward and emergency department with experience of caring for patients with hip fractures treated with FNBs were interviewed. The interviews were audio-recorded, transcribed and analysed using qualitative content analysis. Results: The results in paper I showed that patients who received an FNB assessed lower pain scores over a period of 12 hours. Patients required smaller amounts of opioids and the number of patients requiring opioids was reduced compared with the group that received opioids alone. Overall, in paper II was it a high incidence of complications, common complications in both groups were pre and postoperative delirium (44% and 73%), nutritional problems (71%), anaemia (66%), constipation (64%) and urinary tract infection (45%), but no statistical difference was found between groups of those complications. The results in paper II showed that 39% of the patients who received an FNB and 49% of those who received opioids developed delirium before surgery, with no statistical difference. In paper III, patients described how the pain before surgery was experienced from no pain, to the worst possible pain and everything in between. They described how they dealt with pain in their own way, but also how they felt dependent on the staff's willingness to relieve the pain. They described that the pain treatment could be lifesaving, but that it could also create the feeling of a near-death experience. Further, some patients experienced memory loss regarding the time before surgery, which made it difficult to remember the pain and pain treatment they received. Finally, in paper IV, the staff described that the FNB setting the agenda when caring for older patients with hip fracture in the preoperative phase. Nursing care required timing, with a need of staff orienting to time and customizing their communication. The outcome of the FNB affected nursing care, depending on if the FNB was successful or not successful. Further, staff faced ethical challenges regarding doing good and not harm and relieving pain and avoiding side-effects. Conclusion: This thesis shows that FNB is a feasible preoperative pain management for patients with a hip fracture, even among those with dementia. Evidence-based guidelines are necessary as a basis for assessing pain and providing pain management, but staff should add an individualized pain management approach. Staff should evaluate every patient and see each patient as a unique individual with different experiences of pain and pain management to successfully relieve pain among patients with a hip fracture.
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| 10. |
- Wanselius, Marcus
(författare)
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Development and characterization of an in vitro method for interaction studies between polymers and pharmaceuticals : Aiding in the development of new drug delivery systems
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Polymers are a group of macromolecules used in formulations of pharmaceuticals, one example being the delivery system DC Bead™. Further, some of the most abundant and for drug delivery important constituents of the subcutaneous tissue are charged polymers (polyelectrolytes), e.g. collagen, hyaluronic acid, and chondroitin sulfate. The interactions between these subcutaneous polyelectrolytes and drug molecules are believed to heavily affect the transport and absorption of subcutaneously injected drugs. To increase the understanding of how the interactions between subcutaneous polymers and drug molecules affect the pharmaceutical behavior in subcutaneous tissue, we developed a new microfluidic-based platform. The platform is used to study interactions between polyelectrolytes and drug molecules, and can beyond the investigation of subcutaneous interactions be used to develop polyelectrolyte-based microgel formulations. In this thesis, the microfluidic method denoted “Microfluidic chip for interactions studies” (MIS) is presented, and the design, validation, and several examples of usage are described. The method which is based on microfluidic instrumentation, utilizes spherical microgels created using different types of polymers/polyelectrolytes. These hydrogels collapse when experiencing attractive interactions with drug molecules making it possible to investigate drug binding by studying the volume change of the microgels. We prove that the interactions are strongly affected by charges both on the gel networks and the drug molecules. Further, the aggregation behavior of drugs in a polyelectrolyte-rich environment is studied in detail. Results show that both a strong aggregation behavior and a high charge on the drugs may affect the transport through a network of polyelectrolytes. The behavior of drugs in subcutaneous polyelectrolyte-rich environments such as hyaluronic acid networks, can partly explain bioavailability and absorption rates of the drugs in vivo. Several potential drug delivery systems in the form of microgels were investigated together with both small amphiphilic molecules and larger peptides exhibiting a wide range of physicochemical properties. The results indicate a possibility of delivering large amounts of drug in low volumes of microgel suspensions but with varying release times, ranging from seconds to days. The MIS was able to provide information about the interactions in a large number of polyelectrolyte-drug systems. The studies were performed in a highly efficient and cost-effective way, with experiments being mostly automated. This makes it a suitable method for rapid screening experiments in the development of new microgel formulations, and as part of larger studies utilizing several different methods to better understand and predict the behavior and absorption profiles of potential subcutaneously administrated drugs.
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