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1.
  • Garoff, Maria, 1979- (författare)
  • Carotid calcifications in panoramic radiographs in relation to carotid stenosis
  • 2016
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Calcifications in carotid atheromas can be detected in a panoramic radiograph (PR) of the jaws. A carotid artery calcification (CAC) can indicate presence of significant (≥ 50%) carotid stenosis (SCS). The aim of this thesis was to (1) determine the prevalence of SCS and burden of atherosclerotic disease among patients revealing CACs in PRs, (2) determine the prevalence of CACs in PRs among patients with SCS, (3) analyze whether the amount of calcium and/or (4) the radiographic appearance of the CACs, can improve the positive predictive value (PPV) for SCS detection among patients with CACs in PRs.The thesis is based on four cross-sectional studies. Two patient groups were prospectively and consecutively studied. Group A represented a general adult patient population in dentistry examined with PR presenting incidental findings of CACs. These patients were examined with carotid ultrasound for presence or absence of SCS and their medical background regarding atherosclerotic related diseases and risk factors was reviewed. An age and gender matched reference group was included for comparisons. Group B comprised patients with ultrasound verified SCS, examined with PR prior to carotid endarterectomy. The PRs were analysed regarding presence of CACs. The extirpated plaques were collected and examined with cone-beam computed tomography (CBCT) to determine the amount of calcium. The radiographic appearance of CACs in PRs from Group A and B were evaluated for possible association with presence of SCS.In Group A, 8/117 (7%) of patients with CAC in PRs revealed SCS in the ultrasound examination, all were found in men (8/64 (12%)). Patients with CACs in PRs revealed a higher burden of atherosclerotic disease compared to participants in the reference group (p <0.001). In Group B, where all patients had SCS, 84% revealed CACs in PRs and 99% of the extirpated plaques revealed calcification. CACs with volumes varying between 1 and 509 mm3 were detected in the PRs. The variation in volume did not correlate to degree of carotid stenosis. The radiographic appearance that was most frequently seen in neck sides with SCS (65%) was also frequently found in neck sides without SCS (47%) and therefore the PPV did not improve compared to the PPV solely based on presence of CACs.CACs in PRs are more associated with SCS in men than in a general population and patients with CACs in PRs have a higher burden of atherosclerotic disease. The majority of patients with SCS show CACs in PRs and the majority of extirpated carotid plaques reveal calcification. The volume of CAC and specified radiographic appearance does not increase the PPV for SCS in patients with CACs in PRs. In conclusion patients with CACs in PRs, and without previous record of cardiovascular disease, should be advised to seek medical attention for screening of cardiovascular risk factors.
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2.
  • Hägglund, Patricia, 1989- (författare)
  • Swallowing dysfunction among older people in short-term care : prevalence, effect of intervention, and risk of mortality
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Objectives: Swallowing dysfunction (dysphagia) is a common, but often neglected condition among geriatric patients that can cause severe complications such as malnutrition, aspiration pneumonia and death. The aims of this thesis were to (i) describe the study design and method of the multidisciplinary and multicenter project SOFIA (Swallowing function, Oral health, and Food Intake in old Age), (ii) study the prevalence of and the relationship between swallowing dysfunction and risk of undernutrition among older individuals in short-term care, (iii) study the effect of oral neuromuscular training on swallowing dysfunction among older individuals, and (iv) to investigate the association between poor oral health, swallowing dysfunction and mortality.Methods: This thesis includes four original papers that are all part of the SOFIA project. Paper Iis the study protocol. In total, 391 individuals aged 65 or older, from 36 short-term care units were included in the project. At baseline the participants’ status regarding swallowing function (assessed with the Timed Water Swallow Test, TWST), oral health (using the Revised Oral Assessment Guide, ROAG) and nutrition (assessed with the Minimal Eating Observation and Nutrition Form-version II, MEONF-II) were assessed and collected by calibrated professionals. Clinical data were also collected. Paper IIwas a cross-sectional study where the baseline assessments of the participants’ swallowing function and nutritional status were obtained and the relationship analyzed. Paper IIIwas a cluster randomized, controlled trial (cRCT) that included 116 participants identified with swallowing dysfunction in paper II. These participants were randomly assigned to either usual care (control group) or oral neuromuscular training (intervention group). All participants were assessed at baseline, after five weeks’ training and six months after end-of-treatment, regarding swallowing function and swallowing-related quality of life (QOL). Paper IVwas a prospective cohort study where all participants were followed-up 1-year after inclusion to investigate risk factors for mortality by analysis of the associations between swallowing dysfunction, poor oral health, and 1-year survival. Results: Paper II:The median age of the 391 participants was 84 years (Interquartile range [IQR] 11) and 209 (53%) were females. In total, 248 of the 385 (64%) participants showed swallowing dysfunction, and risk of undernutrition was observed in 91 of 390 (23%) participants. The adjusted logistics regression model revealed that participants with swallowing dysfunction had significantly higher odds of undernutrition than those with normal swallowing (Odds ratio [OR]: 1.74, 95% Confidence interval [CI] 1.04 to 2.92, P=0.034).Paper III: At end-of-treatment, a linear mixed model showed significant between-group differences of changes in swallowing efficacy between baseline and after completed treatment period (Ratio 1.60, 95% CI 1.15 to 2.29, P=0.007); indicating a 60% higher swallowing efficacy in the intervention group compared with the control group. Paper IV: A mixed effects Cox model showed that swallowing dysfunction and poor oral health were both independently associated with 1-year mortality (adjusted Hazard Ratio [aHR]: 1.67, 95% CI 1.02 to 2.75,P=0.041 and aHR: 1.98, 95% CI 1.07 to 3.65, P=0.029, respectively). In addition, swallowing dysfunction and poor oral health in combination predicted the highest mortality rate (35%, P<0.001).Conclusion: Swallowing dysfunction is highly prevalent and a risk factor for undernutrition among older people in short-term care. Oral neuromuscular training improves swallowing dysfunction and is thus a promising method of swallowing rehabilitation for older people with impaired swallowing. Swallowing dysfunction and poor oral health are independent risk factors for 1-year morality among older people in short-term care. Therefore, systematic screening and intervention to improve swallowing dysfunction and poor oral health are important to achieve healthy aging and to prevent undernutrition and early death.
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3.
  • Isehed, Catrine, 1958- (författare)
  • Peri-implantitis : treatment and effects of enamel matrix derivative
  • 2018
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Biological complications affecting osseointegrated dental implants are a growing treatment problem in clinical practice. Since the number of implant carriers has increased in recent decades, this is an urgent topic in dentistry. Peri-implantitis, inflammatory degradation of the implant-supporting jawbone, affects approximately 20% of all implant carriers and approximately 10% of all implants.Implant surfaces are colonised by microbes that may cause an inflammatory process in the soft tissue around the implant. In some sensitive individuals, the inflammatory response leads to disturbed jawbone remodelling, with increased recruitment and activity of bone-resorbing osteoclasts, which could ultimately lead to implant loss. The corresponding degradation of the bone supporting the teeth is denoted as periodontitis. The current view is that factors such as proinflammatory cytokines and prostaglandins, produced by leukocytes and cells of mesenchymal origin in the inflamed connective tissue, are responsible for local osteoclast recruitment and activation. Pro-inflammatory factors and tissue degradation products will leak into the exudate in the peri-implant sulci and the gingival pockets around the teeth. Analysis of the exudate could be of use for predicting and monitoring peri-implantitis, as well as identifying new targets for treatment.The standard treatment for peri-implantitis is surgery in combination with mechanical cleaning of the implant surface and optimisation of oral hygiene, with the goal of achieving infection control and pocket reduction. This treatment has a moderate effect on healing of the peri-implantitis lesion around the dental implant. The use of adjunctive bone grafts, membranes and antimicrobials has thus far not been shown to achieve a more successful outcome. Adjunctive treatment with enamel matrix derivative (EMD) during regenerative periodontal surgery contributes to wound healing and increased tissue support, but the adjunctive effect of EMD during surgical treatment of peri-implantitis remains unknown.The overall aim of this thesis was to investigate the outcome of a regenerative surgical treatment approach with and without adjunctive EMD treatment from the short- and long-term perspectives and to increase our knowledge of microbial flora and biomarkers in the peri-implant sulci before and after treatment. Furthermore, an additional aim of this work was to investigate whether EMD could directly affect osteoclast formation and activity.We performed a randomised controlled clinical trial of a surgical intervention for peri-implantitis with and without EMD. In multivariate modelling, an increased marginal bone level at the implant site 12 months after surgery was significantly associated with EMD, the number of osseous walls in the peri-implant bone defect and a gram-positive/aerobic microbial flora, whereas a reduced bone level was associated with a gram-negative/anaerobic microbial flora and the presence of bleeding and pus, with a cross-validated predictive capacity (Q2) of 36.4%. Similar trends were observed for bone level, pocket depth, plaque, pus and bleeding, but these associations were statistically non-significant in the univariate analysis. Five years after treatment, no significant differences in bone level changes were observed between groups, but fewer implants were lost to follow-up due to reinfections in the EMD-treated group.We used mass spectrometry to analyse the protein content in peri-implant crevicular fluid (PICF) before and up to 12 months after treatment. The total protein amount and diversity displayed decreasing trends 3, 6 and 12 months after treatment. Multivariate analysis of the PICF protein content revealed two major groups, cluster 2 and cluster 3, of which cluster 2 was associated with an increased risk of implant loss. EMD treatment was associated with cluster 3, which was in turn associated with increased implant survival.To test whether EMD affects osteoclast formation or bone resorption, we added purified EMD to RANKL-stimulated mouse bone marrow macrophage cultures in plastic dishes and counted the number of osteoclasts. We also cultured the cells on bone slices and measured the secretion of TRAP5b and the release of CTX-1 into the culture medium as biomarkers of osteoclast numbers and bone resorption, respectively, but no effect of EMD was observed.In conclusion, adjunctive EMD during surgical treatment of peri-implantitis changed the microbial flora to a less pathogenic microbiota, and similar changes in the inflammatory protein profile of PICF were observed; these effects were associated with implant survival. However, the trend toward a positive healing response after EMD treatment was not associated with a significant radiographic bone gain in this study and needs to be further explored. In addition, our finding that EMD did not affect osteoclast formation or bone resorption in vitro indicates that the effect of EMD on bone regeneration, as seen in periodontitis treatment, does not seem to depend on a direct inhibitory effect on osteoclast formation or bone resorption.
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4.
  • Kindstedt, Elin, 1991- (författare)
  • Novel Insights into Inflammatory Disturbed Bone Remodelling
  • 2017
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Bone is a dynamic tissue that is continuously remodelled, a process that requires equal amounts of osteoclastic bone resorption and osteoblastic bone formation. Inflammation may disturb the equilibrium and result in local and/or systemic bone loss. Negative bone mass balance occurs in several chronic inflammatory diseases, e.g. periodontitis and rheumatoid arthritis (RA). The aetiology of periodontitis is infectious, while RA is an autoimmune disease. Despite aetiological differences, an association between the two diseases has been established but it is not known if they are causally related. Periodontitis may develop when the inflammatory process, initially restricted to the gingiva (gingivitis), further invades the periodontium and causes bone resorption. The cellular and molecular mechanisms underlying the transition from gingivitis to periodontitis are not fully elucidated. Osteoclast formation is dependent on receptor activator of nuclear factor kappa B ligand (RANKL), but how osteoclast precursors are recruited to the jawbone is poorly understood. A family of cytokines named chemokines has been reported to possess such properties and increasing evidence points towards their involvement in the pathogenesis of chronic inflammatory diseases.The overall aim of this thesis was to gain extended knowledge about the role of chemokines and a newly discovered family of leukocytes named innate lymphoid cells (ILCs) in periodontitis and concomitant inflammatory disturbed bone remodelling. Furthermore, the aim was also to study the association between periodontitis and RA.We identified increased serum levels of monocyte chemoattractant protein (MCP)-1 and CCL11 in individuals with periodontitis. Moreover, a robust correlation between the two chemokines and periodontitis was detected in a weighted analysis of inflammatory markers, subject characteristics and periodontitis parameters. We detected higher MCP-1 levels in periodontitis tissue compared to non-inflamed. Furthermore we demonstrated that human gingival fibroblasts express MCP-1 and CCL11 in response to pro-inflammatory cytokines through NF-κB signalling. Using an inflammatory bone lesion model and primary cell cultures, we discovered that osteoblasts express CCL11 in vivo and in vitro and that the expression increased under inflammatory conditions. Osteoclasts did not express CCL11, but its high affinity receptor CCR3 was upregulated during osteoclast differentiation and found to co-localise with CCL11 on the surface of osteoclasts. Exogenous CCL11 was internalised in osteoclasts, stimulated the migration of osteoclast precursors and increased bone resorption in vitro.To analyse if periodontitis precedes RA we analysed marginal jawbone loss in dental radiographs taken in pre-symptomatic RA cases and matched controls. The prevalence of jawbone loss was higher among cases, and the amount of jawbone loss correlated with plasma levels of RANKL.In the search of the newly discovered ILCs, we performed flow cytometry analyses on gingivitis and periodontitis tissue samples. We detected twice as many ILCs in periodontitis as in gingivitis. In addition we found RANKL expression on ILC1s (an ILC subset).In conclusion, we demonstrated that CCL11 is systemically and locally increased in periodontitis and that the CCL11/CCR3 axis may be activated in inflammatory disturbed bone remodelling. We also found that marginal jawbone loss correlated with plasma levels of RANKL and preceded clinical onset of symptoms of RA. Furthermore, we demonstrated that ILCs are present in periodontitis and represent a previously unknown source of RANKL. 
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5.
  • Lampa, Ewa, 1956- (författare)
  • Pain and disability in the jaw and neck regions after whiplash trauma : a short- and long-term perspective
  • 2018
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Whiplash trauma, a hyperextension-flexion trauma to the neck that is often related to a car accident, affects tens of thousands in Sweden every year. A significant proportion will develop long-term symptoms including neck pain and dysfunction – this is embraced as Whiplash associated disorders (WAD). Some individuals also develop pain and dysfunction in the orofacial region that is denoted as Temporomandibular disorder (TMD). TMD is common in the population with a prevalence of about 10% but the relation to whiplash trauma is still unclear. The limited number of prospective studies on TMD after whiplash trauma show diverging results, but it has been suggested that TMD develops over time and not in close proximity to the trauma. Prospective studies are needed to determine the course of jaw pain and disability after whiplash trauma.The general aim of this thesis was to evaluate the presence and course of pain and disability in the jaw and neck regions at the acute and chronic stages after whiplash trauma.This prospective cohort study included at baseline 176 cases with a recent whiplash trauma, and 116 age and gender matched controls without a history of neck trauma that were recruited from the general population. The cases had visited the emergency department at Umeå university hospital, Sweden, with neck pain within 72 hours following a car accident and had been diagnosed with neck distortion by a physician. The cases were examined within one month after the trauma (December 2010 to January 2016) and at a 2-year followup (December 2012 to January 2018). All participants completed questionnaires regarding pain and disability in the jaw and neck regions, physical symptoms (pain and non-pain items), and depression. At baseline, 80 of the cases and 80 of the controls also completed a 5-minute chewing capacity test. At the 2- year follow-up, 119 cases (68%) and 104 controls (90%) were re-examined with the same questionnaires.Compared to controls, within one month after a whiplash trauma cases reported significantly more pain in the jaw and neck regions with a positive correlation between the intensity of pain in these regions (Paper I). In the acute stage after trauma, cases, compared to controls, showed a reduced chewing capacity, and this was related to the severity of neck disability (Paper II). For cases, jaw and neck pain correlated positively to each other, to non-specific physical symptoms, and to depression at both the acute (Paper III) and chronic stages (Paper IV). About one third (34%) of the cases reported orofacial pain at baseline, and for a majority of these, the pain persisted at the 2-year follow-up (Paper IV).The presence of orofacial pain early after a whiplash trauma indicates involvement of central sensitization and spread of pain between the jaw and neck regions. The positive correlations between pain in the jaw and neck regions, and to psychosocial factors, underline the integration of these regions and the importance of a biopsychosocial perspective. The impaired jaw function shortly after a neck trauma further underlines the close sensorimotor relationship between the trigeminal and cervical regions. The finding that orofacial pain is common shortly after whiplash trauma, and often persists into the chronic stage, indicates that assessment in the acute stage should include both the neck and jaw regions. From this, it follows that multidisciplinary teams that entail both medical professions and dentists specialised in orofacial pain can be beneficial in the early assessment after whiplash trauma.
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6.
  • Lövgren, Anna, 1979- (författare)
  • Recognition of Temporomandibular Disorders : validity and outcome of three screening questions (3Q/TMD)
  • 2017
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background Pain and dysfunction in the temporomandibular region (Temporomandibular Disorders, TMD) are common conditions in the general population with an estimated treatment need of 5-15% in the general population. However, in Sweden, traceable performed treatments are significantly lower. The reasons for this indicated under-treatment are not known. To easily detect patients with a potential TMD related condition, three screening questions, 3Q/TMD, have been introduced. The aim with this project was to evaluate the validity and outcome of the 3Q/TMD with the objective to recognize individuals with TMD and potential treatment need in the Public Dental Health service (PDHS).Methods The thesis is based on four study samples; three from the PDHS in the county of Västerbotten, Sweden and one sample from the specialized orofacial pain clinic at the Academic Centre for Dentistry, ACTA, Amsterdam, the Netherlands. The bases for all studies are individuals’ answers to the 3Q/TMD and quantitative approaches were used in the analyses. The prevalence of affirmative answers was evaluated in a large cross-sectional study over the lifespan. The validity of the 3Q/TMD in relation to the Diagnostic Criteria for TMD (DC/TMD) as reference standard was established in two case-control studies. The outcome of the 3Q/TMD on TMD treatment within general practice was evaluated in a cohort study.Results Affirmative answers to the 3Q/TMD increased during adolescence. Women answered affirmatively to the 3Q/TMD significantly more often compared to men for all age groups expect for the first and last parts of a one hundred-year lifespan. The highest prevalence was reported by women during their fertile period in life. In a general population sample, 74% of individuals with an affirmative answer qualified for a DC/TMD pain or dysfunctional diagnosis, as compared to 64% in a specialist patient sample. In the general population sample, for the individual 3Q/TMD questions, as well as combinations of questions, the negative predictive values were high (0.92-0.99). For the specialist sample, when at least one question was answered affirmatively the negative predictive value was high (0.90). The positive predictive value was high (0.89) when all three questions were positive. There was significantly more treatment performed or recommended for 3Q-positives (21.5%) compared to 3Q-negatives (2.2%) (P<0.001). The odds ratio for TMD-related treatment for 3Q-positives versus 3Q-negatives was 12.1 (95% CI: 6.3-23.4).Conclusion The 3Q/TMD is a convenient and valid tool to recognize individuals who would benefit from a further TMD examination within an adult, general population. Within specialized orofacial pain clinics, the questions are useful as guidance for further diagnostics. Although the 3Q/TMD was a factor related to TMD treatment, the majority of individuals with self-reported symptoms of TMD still did not receive traceable assessment or treatment. Factors associated with dentists’ clinical decision-making in relation to TMD warrants further research. The utilization of the 3Q/TMD as a part of a decision tree for the clinician can improve the health care for patients with TMD and is therefore recommended within dentistry. 
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7.
  • Mårell, Lena, 1957- (författare)
  • A multidisciplinary study of patients with signs or symptoms attributed to dental restorative materials
  • 2016
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Anxiety for adverse health effects attributed to dental restorative materials especially dentalamalgam, have been discussed extensively off and on the last 30 years. The possible health effect ofamalgam and health effect of replacements of amalgam, have been extensively studied but theresults are inconclusive and the etiology of the reactions are not entirely elucidated. Furthermore,the question of psychological influence on symptoms attributed to dental restorative materials hasbeen raised and need further examination.The aims of this thesis were to describe the change in health over time for patient with symptomsattributed to their dental materials and to determine whether replacement of their dentalrestorative materials had any impact on their perceived health. Furthermore, to determine anddescribe the personality, self-image, level of psychological symptoms and stress among thesepatients and compare the results with those of healthy controls. Finally, to evaluate regression ofLichenoid Contact Reactions and Oral lichen Planus after replacement of the dental materials.A questionnaire was mailed to 614 patients that had been referred to the School of Dentistry, Umeå,Sweden with symptoms attributed to dental materials. Among these patients a subgroup with orallichen also underwent a clinical examination at follow-up.The result showed that patients with complex symptoms had a more unfavorable long-termprognosis concerning persistent complaints than those with local symptoms only. The oralsymptoms had decreased between baseline and follow-up and the general symptoms had increased.The increase in general symptoms was contradictory since many patients experienced healthimprovement after removal of their dental restorative materials. Concerning personality thepatients was characterized mainly by high persistence and by high fatigability and asthenia as wellas psychosocially learned high self-acceptance. Regarding self-image, both patients with LocalSymptoms Only and patients with Multi Symptoms, scored significantly higher on "spontaneous"and "positive self-image" than the reference group. The Multi symptoms group scored significantlyhigher on psychological symptoms compared to the reference group. However, the Local symptomsgroup did not differ from the references. The remission of oral lesions was after an exchange ofdental materials was seen to a greater extent in patients with Lichenoid Contact Reaction than inpatients with Oral Lichen Planus. Regarding psychological parameters, there were no significantdifferences between the groups.In conclusion symptoms related to dental restorative materials seem to be multi-factorial wheredental, medical, social, and psychological factors may be involved. Patient with complex symptomshave a more unfavorable prognosis than patient with local symptoms only. Patient with symptomsself-related to their dental materials may feel improvement in general health after an exchange ofdental materials. The group of patients seems to represent personalities that could be vulnerable inthe demanding modern society, and the various mental and somatic symptoms can be interpretedas attributed to dental fillings. Patients with Local Symptoms or Multi Symptoms are equalconcerning self-image, they are impulsive with an elevated positive self-image, that can result indifficulties in setting limits. Thus in combination with high demands may result in mental stress.The Multi Symptoms group was more psychologically stressed than the group with Local SymptomsOnly and the references. Therefore, before an exchange of dental materials is commenced inpatients with oral lichenoid lesions, a correct diagnosis is needed.
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