Prospective study on health-related quality of life, oral mucositis and oral health on during treatment of head and neck cancer.

BACKGROUND: Few studies have examined health related Quality of Life (HR-QoL) during the treatment of head and neck cancer (HNC) with even fewer focusing on the impact of oral mucositis (OM) on HR-QoL. Studies performed during treatment of HNC makes it possible to follow fluctuations in HR-QoL, OM and other treatment related side effects. The aim was to prospectively analyze HR-QoL, changes in clinical variables and the impact of OM on HR-QoL during HNC treatment. MATERIALS AND METHODS: Patients were recruited before commencing curative cancer treatment and were given professional oral care weekly during oncologic treatment. HR-QoL was reported before, during (week 2, 4 and 6) and three months after treatment using the EORTC Quality of Life questionnaires C30 and H&N35 and the stimulated whole salivary secretion rate was determined at the same time-points. OM (erythema and ulceration) was registered using the Oral Mucositis Assessment Scale (OMAS), at baseline, weekly during treatment and post treatment. Differences in HR-QoL between different timepoints were analyzed. To analyze the impact of OM on HR-QoL the patients were categorized into two groups: no/mild OM (OMAS ulceration score 0-1) or severe OM (OMAS ulceration score ≥ 2) and HR-QoL was compared between the two OM groups at three timepoints during treatment. RESULTS: Fifty-seven patients (43 men, 14 women), with a mean age of 58 years were included. Patients reported progressively impaired HR-QoL, with peak issues noted at weeks 4 and 6, particularly in social eating, senses, appetite loss, sticky saliva, and decreasing salivary secretion rates were determined. Patients with severe OM reported worse HR-QoL compared to those with no/mild OM. Persistent problems 3 months post treatment were appetite loss, dry mouth, senses (smell and taste) and problems with social eating. CONCLUSION: Patients experienced exacerbated symptoms and problems weeks 4 and 6 of oncological treatment, especially among those with severe OM, stressing the importance of clinically monitoring the patients to reduce and alleviate their symptoms. Persistent problems three months post treatment are likely associated with the reduced salivary secretion rate indicating that patients should be monitored also after completed oncological treatment.

Adolescents' self-reported experiences following a person-centred, theory-based educational intervention versus conventional education for improved oral hygiene: Analysis of secondary outcomes of a randomized field study.

AIM: To analyse adolescents' self-reported experiences and behavioural outcomes of a person-centred, theory-based intervention in comparison with conventional information/instruction for improved oral hygiene. MATERIALS AND METHODS: Data were derived from a prospective, multi-centred, two-arm, quasi-randomized field study focusing on the effectiveness of educational interventions for improved oral hygiene. Dental hygienists working within the Public Dental Service, Västra Götaland, Sweden, provided treatments, and adolescents with poor oral hygiene conditions were eligible for participation. The person-centred test intervention was based on social cognitive constructs, and motivational interviewing was used as an approach in communication. The control intervention included conventional information/instructions. Clinical examinations were performed, and questionnaires were distributed at baseline and at 6 months. Three-hundred and twelve patients were enrolled, and data from 276 patients, following treatment per protocol, were analysed. RESULTS: The test group was more satisfied with the education about gingivitis (very good: 61% vs. 37%) and communication during therapy (very good: 69% vs. 50%) and reported to a larger extent that they were much more careful regarding their oral hygiene after the treatment (30% vs. 15%) and had higher confidence about keeping up healthy gingival conditions, in comparison with the control group (all p < .01). CONCLUSIONS: The person-centred, theory-based intervention was superior in terms of adolescents' experiences of education and communication during therapy and self-reported oral hygiene behavioural outcomes at 6 months, in comparison with conventional information/instruction.

Onset of periodontitis - a registry-based cohort study.

OBJECTIVES: The present retrospective registry-based cohort study aimed to identify parameters associated with the onset of periodontitis in young adults. MATERIAL AND METHODS: A total of 345 Swedish subjects were clinically examined at age 19 years (as part of an epidemiological survey) and then followed up to 31 years through the Swedish Quality Registry for Caries and Periodontal diseases (SKaPa). The registry data including periodontal parameters were obtained for the period 2010-2018 (23-31 years). Logistic regression and survival models were used to identify risk factors for periodontitis (PPD ≥6 mm at ≥2 teeth). RESULTS: The incidence of periodontitis during the 12-year observation period was 9.8%. Cigarette smoking (modified pack-years; HR 2.35, 95%CI 1.34-4.13) and increased probing pocket depth (number of sites with PPD 4-5 mm; HR 1.04, 95%CI 1.01-1.07) at 19 years were risk factors for periodontitis in subsequent young adulthood. No statistically significant association was identified for gender, snuff use, plaque and marginal bleeding scores. CONCLUSION: Cigarette smoking and increased probing pocket depth (≥4 mm) in late adolescence (19 years) were relevant risk factors for periodontitis in young adulthood. CLINICAL RELEVANCE: Our study identified cigarette smoking and increased probing depth in late adolescence as relevant risk factors of periodontitis in young adulthood. Preventive programs should therefore consider both cigarette smoking and probing pocket depths in their risk assessment.

Legitimizing user knowledge in mental health services: Epistemic (in)justice and barriers to knowledge integration.

Including the voices and knowledge of service users is essential for developing recovery-oriented and evidence-based mental health services. Recent studies have however, suggested that challenges remain to the legitimization of user knowledge in practice. To further explore such challenges, a co-production study was conducted by a team of researchers and representatives from user organizations in Sweden. The aim of the study was to explore the barriers and facilitators to the legitimacy of user knowledge, as a central factor in sustainably implementing user influence in mental health practice. A series of workshops, with representatives of mental health services and user organizations were conducted by the research team to explore these issues. The analysis built on the theoretical framework of epistemic injustice, and the underlying aspects, testimonial, hermeneutic and participation-based injustice, were utilized as a framework for a deductive analysis. Results suggest that this is a useful model for exploring the complex dynamics related to the legitimacy of user knowledge in mental health systems. The analysis suggests that the legitimacy of user knowledge is related to the representativeness of the knowledge base, the systematic formulation of this knowledge in applicable methods, access to resources and positions within the mental health system and participation in the process of integrating this knowledge-base in mental health contexts. Legitimizing user knowledge in practice additionally challenges mental health systems to support readiness for change in working environments and to address the power and role issues that these changes involve.

Implementation of the Recovery Guide in inpatient mental health services in Sweden-A process evaluation study.

BACKGROUND: Involving service users in inpatient care and recovery planning has gained interest worldwide. Our purpose was to evaluate the process of implementation of a coproduced Recovery Guide (RG) intervention in 22 inpatient wards in Sweden, in terms of context, implementation process and mechanisms of impact over 12 months. METHODS: A mixed method design and a process evaluation framework were used to guide data collection and to deductively analyze perspectives and descriptive statistics of delivery from three stakeholder groups. RESULTS: Results showed that although initial contextual barriers were present (e.g., lack of resources, and interest, uncertainty in the organization, a dominant illness perspective), it was possible to implement the RG in 14 wards, where 53% of admitted service users received the intervention. Legitimacy of the intervention, engaged managers and staff, capacity of staff and ward organization, coproduction and continuous support from user organization were critical mediators. Mechanisms of impact concerned (1) a new perspective on mental health, well-being and recovery, (2) capacity building of a recovery approach in inpatient settings and (3) a meaningful outlet for users' thoughts and feelings on recovery, sharing narratives and influencing care and goals. CONCLUSIONS: The RG intervention has the potential to promote a recovery approach in inpatient mental health services (MHSs). Coproduction among stakeholders created trust and a sustainable implementation that made it possible for wards to resume implementation when contextual barriers had been resolved. PATIENT AND PUBLIC CONTRIBUTION: The current study involved stakeholders including a service user organization, the public, first-line managers and staff (including peer support workers) in inpatient and community MHS and researchers, who greatly contributed to the implementation programme, including codesign of the RG intervention as well as coproduction of the implementation in inpatient MHS. All authors have their own lived experiences of mental health problems as a service user or as a relative.

A person-centred, theory-based, behavioural intervention programme for improved oral hygiene in adolescents: A randomized clinical field study.

AIM: To test the effectiveness of a person-centred and theory-based educational intervention to increase adolescents' adherence to adequate oral hygiene behaviour, that is, self-performed periodontal infection control. MATERIALS AND METHODS: Data were derived from a prospective, multi-centred, two-arm, quasi-randomized field study in which treatment was performed by dental hygienists (DHs) within the Public Dental Service, Västra Götaland, Sweden. Adolescents with poor oral hygiene conditions were invited to participate. The test intervention was based on cognitive behavioural theory and principles, and the DHs used a collaborative communicative approach, inspired by motivational interviewing. The control intervention consisted of conventional information/instruction. Clinical assessments and oral hygiene behaviours were evaluated at 6 months. RESULTS: Three-hundred and twelve adolescents were enrolled, of whom 274 followed the treatment to 6-month follow-up. There were significant improvements in gingival bleeding and plaque scores for both treatment groups at 6 months, with significantly greater improvements in the test group. Adolescents in the test group brushed their teeth and used interdental cleaning aids more frequently compared to participants in the control group at 6 months. CONCLUSION: A person-centred and theory-based oral health education programme is more effective than conventional oral health education in improving adolescents' oral hygiene behaviour and periodontal infection control. CLINICALTRIALS: gov (NCT02906098).

Variations in odontological care routines for patients undergoing treatment for head and neck cancer in county councils/regions of Sweden.

OBJECTIVE: To investigate current odontological care routines for patients treated for head and neck cancers in the county councils/regions (C/Rs) of Sweden. METHODS: An invitation to fill in a web-based questionnaire was sent to dentists/dental hygienists working in dental clinics in the 12 C/Rs, treating and responsible for the odontological care of patients undergoing treatment for cancer of the head and neck. The questionnaire started with two mandatory and one non-mandatory questions, followed by questions regarding routines before (n = 28), during (n = 23), and after (n = 9) treatment, plus two additional questions, totalling 65 questions. RESULTS: Four dental hygienists and six dentists in 10 of the 12 C/Rs answered the questionnaire. Three C/Rs stated that they measure both the unstimulated and stimulated salivary secretion rate, and another C/R stated that they measure the stimulated secretion rate only. Similar recommendations were given regarding oral hygiene, salivary stimulants and substitutes, and extra fluoride. However, great variations were seen regarding recommendations for preventing and relieving oral mucositis. There were also discrepancies regarding information about the importance of avoiding smoking and alcohol. In seven C/Rs, patients visited the dental hygienist once a week during cancer treatment. CONCLUSION: The results suggests that there are great variations in odontological care given to patients undergoing treatment for cancer of the head and neck region in different county councils/regions in Sweden. There is a need to develop and implement evidence-based guidelines to decrease the risk of oral complications and increase both the quality of life and the quality of care.

Explorative study on quality of life in relation to salivary secretion rate in head and neck cancer patients treated with radiotherapy up to 2 years post treatment.

OBJECTIVE: The aim of this study was to analyse quality of life (QoL) pretreatment and up to 24 months post radiation therapy (RT) in patients with head and neck (H&N) cancer. METHODS: Twenty-nine patients (19 men and 10 women) with a mean age of 59 ± 8 years were included. The stimulated salivary secretion was measured and the patients completed the European Organisation for Research and Treatment of Cancer Quality of Life questionnaires (EORTC QLQ-C30 and H&N35) and the Hospital Anxiety and Depression scale (HADS) pretreatment and at 6, 12 and 24 months post RT. RESULTS: At all time-points after RT (6, 12, and 24 months), patients with hyposalivation (stimulated secretion rate ≤0.7 mL/min) reported clinically significant differences (> 10 points) regarding insomnia, swallowing, social eating, dry mouth, and sticky saliva. Statistically significant differences were found for emotional functioning and insomnia at 12 months (P < 0.05 for both) and for sticky saliva at both 12 and 24 months (P < 0.05 and P < 0.01). The number of clinically significant differences increased from 10 at both 6 and 12 months post-RT to 14 functioning/symptom scales and single items at the 24 months follow-up. At 24 months post RT, 21% of patients with hyposalivation had HADS scores suggesting anxiety problems compared to 7% for those with stimulated salivary secretion rates >0.7 mL/min. CONCLUSION: Patients with hyposalivation showed deterioration in health related quality of life (QoL) at 24 months compared with 12 months post RT. Most pronounced were problems with insomnia, swallowing, social eating, dry mouth, and sticky saliva.

Immunotherapy targeting α-synuclein protofibrils reduced pathology in (Thy-1)-h[A30P] α-synuclein mice.

Several lines of evidence suggest that accumulation of aggregated alpha-synuclein (α-synuclein) in the central nervous system (CNS) is an early pathogenic event in Parkinson's disease and other Lewy body disorders. In recent years, animal studies have indicated immunotherapy with antibodies directed against α-synuclein as a promising novel treatment strategy. Since large α-synuclein oligomers, or protofibrils, have been demonstrated to possess pronounced cytotoxic properties, such species should be particularly attractive as therapeutic targets. In support of this, (Thy-1)-h[A30P] α-synuclein transgenic mice with motor dysfunction symptoms were found to display increased levels of α-synuclein protofibrils in the CNS. An α-synuclein protofibril-selective monoclonal antibody (mAb47) was evaluated in this α-synuclein transgenic mouse model. As measured by ELISA, 14month old mice treated for 14weeks with weekly intraperitoneal injections of mAb47 displayed significantly lower levels of both soluble and membrane-associated protofibrils in the spinal cord. Besides the lower levels of pathogenic α-synuclein demonstrated, a reduction of motor dysfunction in transgenic mice upon peripheral administration of mAb47 was indicated. Thus, immunotherapy with antibodies targeting toxic α-synuclein species holds promise as a future disease-modifying treatment in Parkinson's disease and related disorders.

Monoclonal antibodies selective for α-synuclein oligomers/protofibrils recognize brain pathology in Lewy body disorders and α-synuclein transgenic mice with the disease-causing A30P mutation.

Inclusions of intraneuronal alpha-synuclein (α-synuclein) can be detected in brains of patients with Parkinson's disease and dementia with Lewy bodies. The aggregation of α-synuclein is a central feature of the disease pathogenesis. Among the different α-synuclein species, large oligomers/protofibrils have particular neurotoxic properties and should therefore be suitable as both therapeutic and diagnostic targets. Two monoclonal antibodies, mAb38F and mAb38E2, with high affinity and strong selectivity for large α-synuclein oligomers were generated. These antibodies, which do not bind amyloid-beta or tau, recognize Lewy body pathology in brains from patients with Parkinson's disease and dementia with Lewy bodies and detect pathology earlier in α-synuclein transgenic mice than linear epitope antibodies. An oligomer-selective sandwich ELISA, based on mAb38F, was set up to analyze brain extracts of the transgenic mice. The overall levels of α-synuclein oligomers/protofibrils were found to increase with age in these mice, although the levels displayed a large interindividual variation. Upon subcellular fractionation, higher levels of α-synuclein oligomers/protofibrils could be detected in the endoplasmic reticulum around the age when behavioral disturbances develop. In summary, our novel oligomer-selective α-synuclein antibodies recognize relevant pathology and should be important tools to further explore the pathogenic mechanisms in Lewy body disorders. Moreover, they could be potential candidates both for immunotherapy and as reagents in an assay to assess a potential disease biomarker.

Behavior of human chondrocytes in engineered porous bacterial cellulose scaffolds.

Regeneration of articular cartilage damage is an area of great interest due to the limited ability of cartilage to self-repair. The latest cartilage repair strategies are dependent on access to biomaterials to which chondrocytes can attach and in which they can migrate and proliferate, producing their own extracellular matrix. In the present study, engineered porous bacterial cellulose (BC) scaffolds were prepared by fermentation of Acetobacter xylinum (A. xylinum) in the presence of slightly fused wax particles with a diameter of 150-300 microm, which were then removed by extrusion. This porous material was evaluated as a scaffold for cartilage regeneration. Articular chondrocytes from young adult patients as well as neonatal articular chondrocytes were seeded with various seeding techniques onto the porous BC scaffolds. Scanning electron microscopy (SEM) analysis and confocal microscopy analysis showed that cells entered the pores of the scaffolds and that they increasingly filled out the pores over time. Furthermore, DNA analysis implied that the chondrocytes proliferated within the porous BC. Alcian blue van Gieson staining revealed glycosaminoglycan (GAG) production by chondrocytes in areas where cells were clustered together. With some further development, this novel biomaterial can be a suitable candidate for cartilage regeneration applications.

Differential input by Ste5 scaffold and Msg5 phosphatase route a MAPK cascade to multiple outcomes.

Pathway specificity is poorly understood for mitogen-activated protein kinase (MAPK) cascades that control different outputs in response to different stimuli. In yeast, it is not known how the same MAPK cascade activates Kss1 MAPK to promote invasive growth (IG) and proliferation, and both Fus3 and Kss1 MAPKs to promote mating. Previous work has suggested that the Kss1 MAPK cascade is activated independently of the mating G protein (Ste4)-scaffold (Ste5) system during IG. Here we demonstrate that Ste4 and Ste5 activate Kss1 during IG and in response to multiple stimuli including butanol. Ste5 activates Kss1 by generating a pool of active MAPKKK (Ste11), whereas additional scaffolding is needed to activate Fus3. Scaffold-independent activation of Kss1 can occur at multiple steps in the pathway, whereas Fus3 is strictly dependent on the scaffold. Pathway specificity is linked to Kss1 immunity to a MAPK phosphatase that constitutively inhibits basal activation of Fus3 and blocks activation of the mating pathway. These findings reveal the versatility of scaffolds and how a single MAPK cascade mediates different outputs.

Effect of different forms of alkali treatment on specific fermentation inhibitors and on the fermentability of lignocellulose hydrolysates for production of fuel ethanol.

Treatment with alkali, particularly overliming, has been widely used as a method for the detoxification of lignocellulose hydrolysates prior to ethanolic fermentation. However, the mechanisms behind the detoxification effect and the influence of the choice of cation have not been well understood. In this study, a dilute acid hydrolysate of spruce and an inhibitor cocktail consisting of six known inhibitors were used to investigate different alkali detoxification methods. The various treatments included the addition of calcium hydroxide, sodium hydroxide, potassium hydroxide, and ammonia to pH 10.0 and subsequent adjustment of the pH to 5.5 with either sulfuric or hydrochloric acid as well as treatment with the corresponding amounts of calcium, sodium, and potassium as sulfate or chloride salts at pH 5.5. An RP-HPLC method was developed for the separation of 18 different inhibitors in the hydrolysate, including furaldehydes and phenolics. Detection and quantification were carried out by means of UV, DAD, and ESI-MS in negative mode. Treatment of the spruce hydrolysate with alkali resulted in up to approximately 40% decrease in the concentration of furaldehydes. The effects on the aromatic compounds were complex. Furthermore, SFE was performed on the precipitate formed during alkali treatment to evaluate the inhibitor content of the precipitate, and the following RP-HPLC analysis implied that potential inhibitors were removed mainly through conversion rather than through filtration of precipitate. Parallel experiments in which sulfuric acid or hydrochloric acid was used for acidification to pH 5.5 after alkali treatment indicated that the choice of anion did not affect the removal of inhibitors. Detoxification with calcium hydroxide and ammonia resulted in better fermentability using Saccharomyces cerevisiae than detoxification with sodium hydroxide. The results from the experiments with the inhibitor cocktail indicated that the positive effects of alkali treatment are difficult to explain by removal of the inhibitors only and that possible stimulatory effects on the fermenting organism warrant further attention.