Patient specific factors predicting adherence and treatment effect of oral appliance therapy in obstructive sleep apnea

The overall objective of this thesis was to generate new knowledge about treatment with mandibular advancement devices (MAD). MAD. Adherence and MAD treatment effects were measured in patients suffering from obstructive sleep apnea (OSA). Continuous positive airway pressure (CPAP) is the first-line treatment for OSA, and only patients who were non-adherent to CPAP were included in this project. The first study assessed the effect of MAD on the apnea/hypopnea index (AHI) of an individually adjusted MAD in patients with moderate(n=82) and severe (n=34) OSA.. Nocturnal respiratory polygraphic recordings (PG) were performed at baseline and 12- month follow-up, and reduction in AHI was the primary outcome for success. The overall treatment success rate was 75%, and there was no significant difference in success rates between the moderate and severe categories. Low pre-treatment oxygen saturation (SpO2 nadir) predicted MAD failure in the multiple regression analysis. The aim of the second study was to test whether a built-in MAD sensor was reliable compared to self-reported MAD use for one month. Patients (n=80) with all grades of OSA were included. The relative reliability was high with an intraclass coefficient (ICC) at r= 0.847. The aim of the third study was to measure AHI change, MAD adherence in patients with all grades of OSA, and to identify partner-specific factors related to adherence. The mean AHI was reduced to half at 8 month follow-up, and sensor-measured adherence rate at follow-up was 60.1%. Mean reduction in AHI was significantly greater in the “good” than in the “poor” adherence group. From the partner perspective, good adherence to MAD was associated with signifigreater positive effects on their relationship and being able to share bedroom again. We conclude that MAD seems to be an effective treatment alternative for all grades of OSA. Low SpO2nadir predicted a poor effect from MAD. Adherence to MAD could be reliably measured with a built-in sensor. MAD adherence is related both to the treatment effect and bedpartners’ motivational influence. Their attitude and support may be a hidden resource for improving adherence to MAD in the treatment of OSA.Doktorgradsavhandlin

Allergisk reaksjon i forbindelse med bruk av søvnapnéskinne

Langvarig behandling med søvnapnéskinner er godt undersøkt i vitenskapelige studier. De viser god effekt mot snorking og pustestopp, og det har fremkommet få bivirkninger (1). CPAP (Continuous Positive Airway Pressure) er regnet som «gullstandarden» i behandling av obstruktiv søvnapné, men på grunn av dårligere compliance med CPAP er en individuelt tilpasset og justerbar skinne (MAD; mandibular advancement device) et godt egnet behandlingsalternativ til CPAP. Søvnapnéskinne viser seg å være effektiv i å redusere alvorlighetsgraden av obstruktiv søvnapné (OSA) og også i å minske de negative helsekonsekvensene av OSA (2).publishedVersio

Protocols and characterization data for 2D, 3D, and slice-based tumor models from the PREDECT project

Two-dimensional (2D) culture of cancer cells in vitro does not recapitulate the three-dimensional (3D) architecture, heterogeneity and complexity of human tumors. More representative models are required that better reflect key aspects of tumor biology. These are essential studies of cancer biology and immunology as well as for target validation and drug discovery. The Innovative Medicines Initiative (IMI) consortium PREDECT (www.predect.eu) characterized in vitro models of three solid tumor types with the goal to capture elements of tumor complexity and heterogeneity. 2D culture and 3D mono-and stromal cocultures of increasing complexity, and precision-cut tumor slice models were established. Robust protocols for the generation of these platforms are described. Tissue microarrays were prepared from all the models, permitting immunohistochemical analysis of individual cells, capturing heterogeneity. 3D cultures were also characterized using image analysis. Detailed step-by-step protocols, exemplary datasets from the 2D, 3D, and slice models, and refined analytical methods were established and are presented.Peer reviewe

Histomorphometric analysis of inflammatory response and necrosis in re-implanted central incisor of rats treated with low-level laser therapy

Low-level laser therapy is a tool employed in the management of post-operative inflammation process and in the enhancement of reparative process. The aim of the study was to perform histological evaluation of dental and periodontal ligament of rats central upper-left incisor teeth re-implanted and irradiated with low-level laser (InGaAl, 685 nm, 50 J/cm2) 15, 30, and 60 days after re-implantation. Seventy-two male rats had the central upper left incisor removed and kept for 15 min on dry gauze before replantation. Laser was irradiated over the root surface and empty alveolus prior replantation and over surrounding mucosa after the re-implantation. After histological procedures, all slices were analyzed regarding external resorption area and histological aspects. We observed an increase of root resorption (p < 0.05) in the control group compared to the laser group at 15, 30, and 60 days. These results showed that the laser groups developed less root resorption areas than the control group in all experimental periods. Additionally, histological analysis revealed less inflammatory cells and necrotic areas in laser groups

Capturing tumor complexity in vitro : Comparative analysis of 2D and 3D tumor models for drug discovery

Two-dimensional (2D) cell cultures growing on plastic do not recapitulate the three dimensional (3D) architecture and complexity of human tumors. More representative models are required for drug discovery and validation. Here, 2D culture and 3D mono-and stromal co-culture models of increasing complexity have been established and cross-comparisons made using three standard cell carcinoma lines: MCF7, LNCaP, NCI-H1437. Fluorescence-based growth curves, 3D image analysis, immunohistochemistry and treatment responses showed that end points differed according to cell type, stromal co-culture and culture format. The adaptable methodologies described here should guide the choice of appropriate simple and complex in vitro models.Peer reviewe

Patient specific factors predicting adherence and treatment effect of oral appliance therapy in obstructive sleep apnea

The overall objective of this thesis was to generate new knowledge about treatment with mandibular advancement devices (MAD). MAD. Adherence and MAD treatment effects were measured in patients suffering from obstructive sleep apnea (OSA). Continuous positive airway pressure (CPAP) is the first-line treatment for OSA, and only patients who were non-adherent to CPAP were included in this project. The first study assessed the effect of MAD on the apnea/hypopnea index (AHI) of an individually adjusted MAD in patients with moderate(n=82) and severe (n=34) OSA.. Nocturnal respiratory polygraphic recordings (PG) were performed at baseline and 12- month follow-up, and reduction in AHI was the primary outcome for success. The overall treatment success rate was 75%, and there was no significant difference in success rates between the moderate and severe categories. Low pre-treatment oxygen saturation (SpO2 nadir) predicted MAD failure in the multiple regression analysis. The aim of the second study was to test whether a built-in MAD sensor was reliable compared to self-reported MAD use for one month. Patients (n=80) with all grades of OSA were included. The relative reliability was high with an intraclass coefficient (ICC) at r= 0.847. The aim of the third study was to measure AHI change, MAD adherence in patients with all grades of OSA, and to identify partner-specific factors related to adherence. The mean AHI was reduced to half at 8 month follow-up, and sensor-measured adherence rate at follow-up was 60.1%. Mean reduction in AHI was significantly greater in the “good” than in the “poor” adherence group. From the partner perspective, good adherence to MAD was associated with signifigreater positive effects on their relationship and being able to share bedroom again. We conclude that MAD seems to be an effective treatment alternative for all grades of OSA. Low SpO2nadir predicted a poor effect from MAD. Adherence to MAD could be reliably measured with a built-in sensor. MAD adherence is related both to the treatment effect and bedpartners’ motivational influence. Their attitude and support may be a hidden resource for improving adherence to MAD in the treatment of OSA

Seterkulturen i Innfjorden. Bevaring av seterkulturen som et helthetlig kulturminne med lokale særegenheter og taus kunnskap

Avhandlingen har som formål å finne mulige handlingsplaner for å bevare seterkulturen som en helhet, inkludert den tause kunnskapen som er i ferd med å dø ut, i det siste generasjon av dem som selv opplevde det snart ikke lever lenger. Avhandlingen kartlegger samtlige setrer i Innfjorden, Rauma kommune, Møre og Romsdal, såvel setrene som fortsatt brukes, setrene som er forlatt og setrene som er tapt. En del av avhandlingens formål, er å gi en fullstendig oversikt over den nødvendige informasjonen om setrenes naturomgivelser og strukturer. I andre del vurderes ulike tiltak for bevaring av nevnte seterkultur, sett opp mot hvilke tiltak som eksisterer i andre deler av landet. Til slutt gis det anbefalinger for hva som kan gjøres for å bevare setrene sett i forhold til hvilken tilstand de er i dag, med mål om å engasjere både vanlige folk, bøndene som bruker og har brukt setrene, og andre interessenter for øvrig

Oral appliance treatment in moderate and severe obstructive sleep apnoea patients non-adherent to CPAP

The aim of this retrospective study was to evaluate the effect of individually adjusted custom-made mandibular advancement device/oral appliance (OA) in treatment of patients with moderate and severe obstructive sleep apnoea (OSA), who were non-adherent to continuous positive airway pressure (CPAP) therapy. During 2007-2013, 116 patients with moderate (n = 82) and severe (n = 34) OSA non-adherent to CPAP treatment were referred for dental management with an individually adjusted OA at a specialist sleep clinic. Ten of the participants (8·6%) were lost to follow-up, leaving the data set to consist of 106 patients (71 men/35 women, mean age 57 year, range 28-90). Nocturnal respiratory polygraphic recordings were performed at baseline and follow-up. Average time between baseline polygraphy and follow-up was 12 months. A successful OA treatment outcome was based on polygraphy at the follow-up and divided into three groups: 1 = AHI 50% reduction in baseline AHI; and 3. >50% reduction in baseline AHI. If there was a ≤ 50% reduction in baseline AHI at the follow-up, the treatment was considered as a failure. The overall treatment success rate was 75%. There was no significant difference in success rates between patients in the moderate and severe categories (69% and 77%, respectively). Low oxygen saturation (SpO2 nadir) had a high predictive value for OA treatment failure. OA treatment of patients non-adherent to CPAP is efficient and especially promising for the severe OSA group who are at greatest risks for developing serious comorbidities, if left untreated

Data from: Ellipsoid segmentation model for analyzing light-attenuated 3D confocal image stacks of fluorescent multi-cellular spheroids

In oncology, two-dimensional in-vitro culture models are the standard test beds for the discovery and development of cancer treatments, but in the last decades, evidence emerged that such models have low predictive value for clinical efficacy. Therefore they are increasingly complemented by more physiologically relevant 3D models, such as spheroid micro-tumor cultures. If suitable fluorescent labels are applied, confocal 3D image stacks can characterize the structure of such volumetric cultures and, for example, cell proliferation. However, several issues hamper accurate analysis. In particular, signal attenuation within the tissue of the spheroids prevents the acquisition of a complete image for spheroids over 100 micrometers in diameter. And quantitative analysis of large 3D image data sets is challenging, creating a need for methods which can be applied to large-scale experiments and account for impeding factors. We present a robust, computationally inexpensive 2.5D method for the segmentation of spheroid cultures and for counting proliferating cells within them. The spheroids are assumed to be approximately ellipsoid in shape. They are identified from information present in the Maximum Intensity Projection (MIP) and the corresponding height view, also known as Z-buffer. It alerts the user when potential bias-introducing factors cannot be compensated for and includes a compensation for signal attenuation

S4_File: 3D image stack, LNCaP cancer spheroids in co-culture with CAFs, control sample (DMSO), well A05, field 3, stack 335

3D image stack of 3D fluorescent multi-cellular spheroid culture existing out of LNCaP human prostate cancer cells (ATCC, Rockville, USA) and CAF-PF179T human cancer associated fibroblasts (a cell line obtained from the Weizmann Institute, via the PREDECT consortium)