| 1. |
- Ali, Abdullah, 1985-
(författare)
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Topical formulations, design and drug delivery : "A dive into water"
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Water is a vital component regulating the properties of topical formulations and their interaction with biological barriers, such as skin and mucosa. Changing the watercontent within the frame of the pharmaceutical triangle will have a huge impact on which type of formulation, such as a cream, ointment, gel, or lotion, is formed, as well as the physical properties of the formulation. The composition of a formulation, and the subsequent reformulation after application, will govern the features of the residual film. This will in turn affect the barrier properties of the underlying tissue and consequently the penetration of various substances across skin or mucosa.The primary aim of this thesis has been to provide further understanding on differences between traditional surfactant-based formulations and particle-stabilized, Pickering, formulations and how specific excipients, like alcohols, emollients, and thickeners can affect their physical and/or sensorial properties. The secondary aim has been to gain more knowledge on the role of water in topical formulations and how it affects the properties of the underlaying tissue on application.By combining a portfolio of physicochemical techniques combined with sensory science, we have been able to identify differences between Pickering and surfactantstabilized formulations. Starch-based Pickering emulsions were perceived as less greasy and sticky than traditional creams, even at high oil content. Moreover, we were able develop a novel type of alcohol-based Pickering emulsion with combined moisturizing and antiseptic properties. We have also been able to link sensory attributes, evaluated by human volunteers, with physicochemical characterizations. Furthermore, the in vitro ForceBoard™ method was developed further and we evaluated its potential to be used as an ex vivo method using excised skin. In addition, we have shown that that the water gradient over a biological barrier has a general relevance with respect to drug absorption and should be considered not only in dermaldrug delivery but also for buccal and nasal drug delivery.
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| 2. |
- Andersson, Lisa
(författare)
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Problematisk opioidanvändning : om opioidrelaterade dödsfall och LARO i södra Sverige
- 2021
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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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| 3. |
- Jankovskaja, Skaidre
(författare)
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Non-invasive monitoring of low molecular weight biomarkers relevant to skin inflammation and cancer
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Development of skin inflammation and cancer in viable epidermis and dermis involve slow molecular weight (LMW) metabolites. We hypothesize that these LMW compounds can be collected on the surface of the skin and used for non-invasive diagnostics of skin disorders. Keeping in mind that substantial transdermal penetrationis achieved only for molecules of < 500 Da, we focused on topical monitoring of LMW biomarkers. In this thesis we investigated non-invasive, topical methods for monitoring LMW biomarkers by relevant in vitro and in vivo experiments. The LMW biomarkers were:- reactive oxygen species (ROS), specifically, hydrogen peroxide, H2O2- amino acids and their derivatives, i.e., tryptophan (Trp), kynurenine (Kyn; a Trpderivative), phenylalanine (Phe), and tyrosine (Tyr; a Phe derivative).Initially, we have carried out in vitro experiments using dermatomed porcine skin and cell cultures. We characterized permeability of the biomarkers through skin and assessed methods of their monitoring. By using Prussian white particles, deposited on porcine skin, we demonstrated that hydrophilic biomarkers, such as H2O2, permeate the skin mainly through hair follicle pathways (Paper I). In paper II, we have showed that the enzymes transforming Trp to the inflammation and cancer biomarker Kyn, are expressed in the basal layer of epidermis. The magnitude of changes of the Trp/Kyn ratio in the cell culture model was assessed. In paper III, we have characterized Trp and Kyn permeability through skin in vitro, concluding that their permeabilities through stratum corneum are comparable. By in vivo experiments outlined in Paper IV, we have demonstrated the feasibility of topical, non-invasive sampling of Trp and Kyn, in relation to other amino acids. Kyn detection was compromised by its low abundance on the skin. In paper V, we performed a proof-of-concept study in vivo and confirmed that non-invasive sampling of Trp and amino acids of similar abundance, such as Phe and Tyr, is more robust. We concluded that Phe/Trp ratio might be equally good biomarker of skin disorders as a predicted Trp/Kyn ratio. Summarizing, the results of this thesis provide basic knowledge for deeper clinical studies of non-invasive, topical sampling of hydrophilic LMW biomarkers of skin inflammation and cancer.
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| 4. |
- Morin, Maxim
(författare)
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Biophysical aspects of the skin barrier : towards increased non-invasive extraction and optimized biomarker sampling
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The skin provides a link to the body’s health via its rich variety of high and low molecular weight biomarkers, reflecting both systemic diseases (e.g., cancer, diabetes) and local skin disorders (e.g., atopic dermatitis, psoriasis). Non-invasive monitoring of disease-specific biomarkers on the skin surface provides a highly attractive diagnostic procedure as alternative to current practices that normally are biopsy-based and invasive. In order to succeed with non-invasive topical diagnostics, the sampling of biomarkers should proceed in a highly accurate and reproducible manner. Further, a major challenge to achieve this goal is to overcome the outermost skin layer (the stratum corneum, SC) that acts as a remarkable permeability barrier, restricting molecular diffusion in and out of our body, including diffusion of potential biomarkers.The primary aim of this thesis is to achieve an optimized and reproducible noninvasive sampling of endogenous biomarkers from the skin surface. Here, water plays a crucial role as the hydration degree of the SC has a strong influence on the diffusion of molecules across the skin barrier. In particular, fully hydrated skin is expected to be optimal for increased diffusion of biomarkers in the skin tissue, favoring efficient extraction.Considering this, to develop a suitable sampling matrix for non-invasive extraction, it is very important to optimize the matrix so that it has a good ability to hydrate the skin as well as a high capacity to absorb the biomarker and finally allow for analytic quantification. The main questions in this thesis are as follows. (i) How long time does it take to reach a stable level of skin hydration? (ii) How do the intrinsic properties of sampling matrices influence the extraction of biomarkers? (iii) What are the effects of the sampling matrices on the biophysical properties of the skin barrier?(iv) Are hydrogels and bicontinuous cubic liquid crystals suitable matrices for noninvasive sampling of endogenous biomarkers? (v) Is reverse iontophoresis a suitable technique to further enhance the extraction endogenous biomarkers?The hydration of the skin is investigated in vivo and in vitro in order to estimate the time to reach stable hydration level. We show that skin hydration proceeds in two distinct stages with different rates of change of the electrical impedance response and conclude that stable conditions are obtained approximately after 60 min of hydration. We explore the novel approach of using lipid-based bicontinuous cubic liquid crystalline phases as matrices for non-invasive sampling of biomarkers in vivo and invitro and compare them with hydrogel-based materials.From these investigations, we conclude that both kind of materials show promising capacity of hydrating the skin and collect skin-derived biomarkers. However, the cubic phases are shown to havea bout twice as high extraction capacity, as compared to hydrogels. Further, we show that reverse iontophoresis enhances extraction of a potential cancer biomarker in vitro by at least an order of magnitude, as compared to passive diffusion. Taken together, the results obtained in this thesis can serve as a point-of-departure for future applications based on non-invasive sampling of disease-related biomarkers from skinin clinical diagnostics.
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| 5. |
- Aghazadeh, Ahmad
(författare)
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Peri-implantitis : risk factors and outcome of reconstructive therapy
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is focused on (I) the outcome of reconstructive treatment of peri-implant defects and (II) risk factors for the development of peri-implantitis.BackgroundAn increasing number of individuals have dental implant-supported reconstructions. The long-time survival rate of dental implants is good, but complications do occur. Accumulation of bacteria on oral implants and the development of a pathogenic biofilm at the mucosal margin will result in inflammatory responses diagnosed as peri-implant mucositis(PiM). Furthermore, PiM may progress to peri-implantitis (Pi) involving the implant-supporting bone and potentially result in a severe inflammatory process resulting in alveolar bone destruction and consequently implantloss. Currently, Pi is a common clinical complication following implant therapy.The prevalence of peri-implantitis has been reported to be around 20 %. Susceptibility to infections and a history of periodontitis are considered as important risk indicators for peri-implantitis. It seems logical that a past history of periodontitis is linked to an increased risk of peri-implantitis. It is possible that other patient-associated factors such as a smoking habit, and presence of general diseases may also be linked to a higher risk for developing peri-implantitis.Treatment of peri-implantitis is difficult. Non-surgical treatment modalities may not be sufficient to resolve the inflammatory process to obtain healthy conditions.Surgical treatment of peri-implantitis has commonly been employed in clinical practice to obtain access to the implant surface thereby increasing the possibility to effectively decontaminate the implant surfaces.The effectiveness and long-term outcomes of reconstructive surgical treatments of peri-implantitis has been debated. The scientific evidence suggests that regular supportive care is an essential component in order to maintain and secure long-term results following treatment of peri-implantitis.Aims1. To assess the short-term efficacy of reconstructive surgical treatmentof peri-implantitis (Study I).2. To analyse risk factors related to the occurrence of peri-implantitis(Study II).3. To assess the importance of defect configuration on the healing response after reconstructive surgical therapy of peri-implantitis (Study III).4. To assess the long-term efficacy of reconstructive surgical treatmentof peri-implantitis (Study IV).MethodsFour studies were designed to fulfil the aims:- A single-blinded prospective randomised controlled longitudinal human clinical trial evaluating the clinical and radiographic results of reconstructive surgical treatment of peri-implantitis defects usingeither AB or BDX.- A retrospective analysis of individuals with either peri-implantitis, or presenting with either peri-implant health, or peri-implant mucositis assessing the likelihood that peri-implantitis was associated with a history of systemic disease, a history of periodontitis, and smoking.- A prospective study evaluating if the alveolar bone defect configuration at dental implants diagnosed with peri-implantitisis related to clinical parameters at the time of surgical intervention and if the short- and long-term outcome of surgical intervention of peri-implantitis is dependent on defect configuration at the time of treatment.- A prospective 5-year follow-up of patients treated either with AB or BDX.Results- The success for both surgical reconstructive procedures was limited. Nevertheless, bovine xenograft provided evidence of more radiographic bone fill than AB. Improvements in PD, BOP, and SUP were observed for both treatment modalities-In relation to a diagnosis of peri-implantitis, a high likelihood of comorbidity was expressed in the presence of a history of periodontitis and a medical history of cardiovascular disease- The buccal-lingual width of the alveolar bone crest was explanatory to defect configuration- 4-wall defects and deeper defects demonstrated more radiographic evidence of defect fill- Reconstructive surgical treatment of peri-implant defects may result in successful clinical outcomes, that can be maintained over at least five years- The use of BDX is more predictable than use of harvested bone from the patient (AB)ConclusionsThe study results suggest that a bovine xenograft provides better radiographic evidence of defect fill than the use of autogenous bone harvested from cortical autologous bone grafts.Treatment with bone grafts to obtain radiographic evidence of defect fill is more predictable at 3- and 4-wall defects than at peri-implantitis bone defects with fewer bone walls.In relation to a diagnosis of peri-implantitis, a high likelihood of comorbidity was found for a history of periodontitis and a history of cardiovascular disease.
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| 6. |
- Boyd, Hannah, 1994-
(författare)
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On the structure and mechanical properties of in vitro salivary pellicles
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Salivary pellicles display exceptional hydration and lubrication performance. At present, there are still gaps in the understanding of how this is achieved. The aim of this thesis was therefore to increase our knowledge on the mechanisms underlying these properties and deepen the understanding of how they are related to the composition and structure of pellicles, with a focus on those formed under in vitro conditions. This has applications ranging from the development of artificial saliva and lubricating coatings for biomedical applications to methodological approaches for initial testing of oral healthcare products. For this, we also focused on developing suitable methodological approaches for these studies, centering on atomic force microscopy, quartz crystal microbalance with dissipation monitoring, ellipsometry and neutron reflectometry techniques, to investigate in vitro and model salivary pellicles.First, we confirmed a two-layer structure for in vitro salivary pellicles and showed that the outer layer is mainly composed by the oral mucin MUC5B, but that it also contains other salivary components that enhance swelling and hydration. In the presence of bulk saliva, the outer layer also contains a reversibly and loosely bound fraction. This fraction increases the adhesiveness of the pellicle but unexpectedly has no significant effect on its lubrication performance. We also investigated the effect of mechanical confinement on model salivary pellicles by means of Neutron Reflectometry, revealing that at a pressure of 1 bar they are already completely compressed and dehydrated. Finally, with the aim to advance towards better oral healthcare products, we investigated the effect of nonionic and amphoteric surfactants on salivary pellicles, showing that they have a gentler effect on pellicle structure than the commonly employed anionic surfactants.
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| 7. |
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| 8. |
- Hylén, Mia, 1975-
(författare)
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Pain in intensive care : assessments and patients’ experience
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of the thesis was to translate, psychometrically test, and further develop the Behavioral Pain Scale for pain assessment in intensive care and to analyze if any other variables (besides the behavioral domains) could affect the pain assessments. Furthermore, the aim was to explore the patients’ experience of pain within the intensive care.The Behavioral Pain Scale (BPS), consisting of the domains “facial expression,” “upper limbs,” and “compliance with ventilator/vocalization,” was translated andculturally adapted into Swedish and psychometrically tested in a sample of 20 patients(study I). The instrument was then further developed within one of the domains and tested for inter-rater reliability, discriminant validity, and criterion validity (study II). The method for analysis in both study I and II was a method specifically developed for paired, ordered, and categorical data. To describe and analyze the process of pain assessment, a General Linear Mixed Model was used to investigate what variables, besides the behaviors, could be associated with the observers’ own assessment of the patients’ pain (study III). Further, the patients’ experiences of pain when being cared for in intensive care were explored (study IV) through interviews with 16 participants post intensive care. Qualitative thematic analysis with an inductive approach was used for the analysis.The first psychometric tests of the BPS (study I) showed inter-rater reliability with agreement of 85%. For the discriminant validity, all domains, except “compliance with ventilator,” indicated discriminant validity.Therefore, in study II, a developed domain of “breathing pattern” was tested alongside the original version. The BPS showed discriminant validity for both the original and the developed version and an inter-rater reliability with agreement of 76-80%. Wheninspecting the respective domains there was a difference in discriminant validity between the original domain of “compliance with ventilation” and the developed domain of “breathing pattern,” showing higher values on the scale for the developed domain during turning. For criterion validity, the BPS showed a higher sensitivity than the observers, who on the contrary had a higher specificity.The General Linear Mix Model (study III) showed that heart rate could be associated with the observers’ assessments of pain. For the behavioral signs, the result indicated that breathing pattern was most associated with the observers’ pain assessment, whilst facial expression did not show any impact on the observers’ assessments.The patients’ experiences of pain (study IV) in intensive care were described as generating a need for control; they experienced a lack of control when pain was present and continuously struggled to regain control. The experience of pain was not only related to the physical sensation but also to psychological and social aspects, along with the balance in the care given, which was important to the participants.In conclusion, the translated and developed version of the Swedish BPS showed promising psychometric results in assessing pain in the adult intensive care patients. Still, other signs, besides behavioral, is possibly used when pain assessing and therefore information about and training in pain assessment are needed to enhance the assessments that are made. Also, the patients’ own experiences highlight the importance of individualizing and adapting pain assessment and treatment to the needs of each patient. Making them a part of the team could enhance their feeling of control, thereby supporting them in facing the experience of pain.
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| 9. |
- Incel, Anil
(författare)
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Amino acid sequence and side chain specific synthetic receptors targeting protein phosphorylation
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Antibodies have become a critical component of many diagnostic assays and are used for therapeutic purposes. Nevertheless they often fail to meet the strict performance demands raised in industry and in the clinic (e.g. stability, reproducibility, selectivity, affinity). These issues are especially notable for assays targeting post translational modifications (PTM) of proteins (phosphorylation, glycosylation, sulfation etc.). Antibody-based technologies suffer from problems of a more general nature associated with the analytical use of biological receptors i.e.: i) limited stability requiring cold chain logistics, ii) high production costs, iii) batch to batch variability. The above emphasizes the need for alternative robust, reproducible and low cost “binders” and assays. The aim in this thesis is to design, develop and test molecularly imprinted polymers (MIPs) which were synthesized epitope and stoichiometric imprinting approaches targeting phosphorylation as a PTM. Protein phosphorylationis one of the most common PTM, which is based on covalent attachment of phosphate group to particular amino acids. Misregulation of phosphorylation process is found related with diseases such as cancer, diabetes, and neurodegeneration. MIPs are synthesized through copolymerization of functional monomers and crosslinkers in the presence of N- and C- terminal protected templates. The key recognition element employed in developed synthetic receptors was 1,3-diaryl urea functionalmonomer 1. This monomer is a potent hydrogen bond donor forming strong cyclichydrogen bonds with oxyanions. Amino acid sequence specific and side chain imprinted binders were prepared targeting phosphorylation on tyrosine (pTyr) and on histidine (pHis). pHis MIP-based approach is proposed as a solution to enrich pHis peptides in the presence of other phosphoesters such as phosphoserine (pSer) in complex mixture without pre-treatment like β-elimination. In pTyr, ZAP-70 (zeta associated 70 kDa protein), which is prognosticator for chronic lymphocytic leukemia (CLL), and pTyr-sequence specific motif Src-SH2 domain were chosen as targets to evaluate regio- or stoichiometric selectivity performance of imprinted polymers. The synthesized polymers are used as effective enrichment tools for target phosphorylated peptides from complex mixture prior to mass spectrometry. Overall, the results demonstrate unique proteomics enrichment tools that link with personalized medicine relying on diagnostic coupled cancer treatment strategies based on kinase inhibitors.
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| 10. |
- Kallunki, Jenny, 1978-
(författare)
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Early Treatment of Class II Malocclusion With Excessive Overjet : evaluating oral health-related quality of life, randomised controlled trials on headgear activator treatment and costs
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Class II malocclusion with excessive overjet is one of the most common malocclusions among children and adolescents. In addition to increasing the risk for dental trauma, the malocclusion can also be related to bullying due to the prominent maxillary incisors. The treatment for a Class II malocclusion can be initiated at different ages and with different treatment strategies, but the treatment timing has often been, and still is, discussed within the orthodontic profession and literature. Research reports that an early treatment approach, initiated in mixed dentition and often including an additional phase of treatment in permanent dentition, reduces the incidence of dental trauma. Otherwise, no differences in treatment effects have yet been seen between treatment that is started early in mixed dentition or treatment initiated later in permanent dentition. During the last decades, there has been an increased focus on patient-reported outcomes within orthodontic research. The patient perspective and economic evaluations of performed treatment are areas where knowledge gaps can be found in the available research. This thesis is based on four studies. The studies were designed with high level of methodology and validity as a priority and with the objective to identify and address knowledge gaps related to the impact of Class II malocclusion with excessive overjet and a subsequent early treatment with headgear activator. Firstly, a systematic review addressing treatment effects was performed. This was followed by the implementation of two randomised controlled trials (RCTs) with the aims to evaluate treatment effects and self-perceived oral health-related quality of life (OHRQoL) as well as the cost associated with treatment. In addition, a clinical controlled trial was performed to assess the self-perceived OHRQoL for children with Class II malocclusion with excessive overjet, and compare to children with unilateral posterior crossbite or normal occlusion with no or mild orthodontic treatment need. The papers referred to in this thesis: Paper I. A systematic literature review performed to evaluate the evidence supporting early treatment (before the age of 10) of Class II malocclusion. The search included four data bases and spanned from January 1960 to October 2017. Paper II. A clinical controlled multicenter trial with the objective to investigate the OHRQoL among 9-year-old children in mixed dentition and to compare the self-perceived OHRQoL by the use of the Child Perceptions Questionnaire (CPQ). Evaluation and comparisons were made for children with Class II malocclusion with excessive overjet (EO), children with unilateral posterior crossbite (UPC), and children with normal occlusion (NO) presenting with no or mild orthodontic treatment need. The sample consisted of 229 children, sourced from 19 Public Dental Service Clinics in Sweden and covering a range of demographic areas.A single centre RCT designed to evaluate the effects of headgear activator treatment and the associated costs forms the basis of the final two papers: Paper III. The effects of early headgear activator treatment was compared to an untreated control group. The sample consisted of 60 children presenting with a Class II malocclusion with excessive overjet. Primary outcome was the reduction of overjet and overbite as well as effects regarding oral health-related quality of life, lip closure, incidence of trauma, and skeletal changes.Paper IV. The costs and treatment effects of headgear activator treatment started in the mixed or late mixed dentition was registered and compared. The sample consisted of 51 children starting treatment at 9 or 11 years of age. The primary outcome measure was comparison of the treatment costs between the two groups. Secondary outcomes were comparisons of oral health-related quality of life, dental and skeletal treatment effects, lip closure, and trauma incidence. The following conclusions were drawn: There is medium to high level of evidence, depending on treatment appliance, that early treatment reduces overjet and improves antero-posterior skeletal relationship, but currently, insufficient evidence is available regarding the effects of early treatment on OHRQoL, incidence of trauma, soft tissue profile, or treatment-related costs. There is a knowledge gap with respect to long-term outcome and the stability of early treatment.Children with Class II malocclusion with excessive overjet report significantly lower self-perceived OHRQoL compared to children with unilateral posterior crossbite or normal occlusion, with the domains of social and emotional well-being being most affected. The children in all three groups reported generally low CPQ scores, which implies an overall fairly good self-perceived OHRQoL.Early treatment with headgear activator was successful in reducing overjet and correcting molar relationship. Early treatment did not result in any significant difference regarding self-reported OHRQoL, lip closure, or incidence of trauma when compared to the untreated control group.The costs associated with headgear activator treatment, as well as the treatment effects, were equivalent regardless of whether treatment was started at 9 or 11 years of age. The most pronounced treatment effects were reduction of overjet and correction of molar relationship, whereas the treatment effects regarding OHRQoL, lip closure, and trauma incidences were found to be modest.With costs and treatment effects being equivalent, an early treatment approach can be advocated to enhance trauma prevention.
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