Patients with rheumatoid arthritis (RA) have a shorter life span than the general population. An increased death due to cardiovascular disease (CVD) has been reported. RA is characterized by synovitis and joint destruction accompanied by an acute phase reaction and systemic features. The present work investigates the epidemiology of CVD in patients with RA in the county of Västerbotten and the influence of inflammation on lipid metabolism and haemostasis. In a retrospective cohort study on 606 RA patients, the overall mortality was significantly higher than in the general population, with an excess death rate for CVD and for ishemic heart diseae (IHD) in both sexes. Multiple Cox regression, showed that male sex, higher age at disease onset and cardiovascular event increased the risk for death. Male sex, high age at disease onset and hypertension increased the risk for cardiovascular event. Diabetes mellitus, treatment with corticosteroids, disease modifying antirheumatic drugs and postmenopausal estrogen neither influenced survival nor the risk of cardiovascular event. In 93 patients with active RA, the levels of cholesterol, high density- (HDL) and low density (LDL) lipoprotein cholesterol were significantly lower, and Lipoprotein(a) was significantly higher compared to controls. In a follow-up on 53 patients, a relation between the change of Lp(a) and acute phase proteins was found only in patients with high levels of Lp(a). Preheparin lipoprotein lipase (LPL) activity and mass were significantly decreased in 17 postmenopausal women with active RA. Preheparin LPL mass correlated inversely to several acute phase proteins and interleukin-6. Low levels of LPL mass may implicate increased hepatic clearence but also increased macrophage ingestion of lipoproteins via the LDL receptor-related protein (LRP). Haemostasis of the circulation was investigated in 74 of the 93 patients with active RA. In patients with extraarticular disease, the release of tissue plasminogen activator (tPA) was significantly decreased, and its inhibitor (PAI-1) was significantly increased compared to patients with nonsystemic disease, implicating hypofibrinolysis. In a two year follow-up, patients with thromboembolic events had significantly elevated levels of von Willebrand factor, PAI-1, triglycerides and haptoglobin compared to event-free patients. In 29 RA patients and 18 spondylarthropathy patients with gonarthritis, radiological joint destruction correlated to PAI-1 antigen in synovial fluid and, inversely, to plasminogen. A relationship between activation of fibrin degrading proteolytic enzymes and joint destruction was implicated. In conclusion, several processes involved in lipid metabolism and haemostasis are influenced in active RA. In view of the increased death rate due to CVD, an efficient control of inflammation should be important, not only for reducing joint destruction, but also for reducing systemical atherogenic and thrombogenic effects. / <p>s. 1-54: sammanfattning, s. 55-133: 6 uppsatser</p> / digitalisering@umu.se

In order to keep the turnaround time it is desirable to have few centrifugal programs and be able to centrifuge microtainer tubes together with vacutainer tubes. BD has launched a new type of microtainer tube that got a lower g-force than the older one on the same centrifugation program. The aims was to compare this program and three other, more powerful, programs and compare the impact on some common analytes and serum indices, especially on hemolysis. Three test parts was performed using venous samples taken from healthy individuals, 1) transfer of whole blood from serum tube to microtainer tubes, a clinical chemistry analysis; 2) whole blood from plasma tube to microtainer tubes, a clinical chemistry analysis and 3) whole blood from plasma tube to microtainer tubes for platelet count analysis. All tubes were examined for gel formation. The result showed a significant variance between some settings for some analytes but foremost at 899g and at 2000g, both in 10 min. The platelet count was below the threshold limit at 2000g. No tube had insufficient formation of the gel. The setting of 2000g was found suitable for microtainer tubes. These results correspond with the recommended settings from BD. Further studies are needed with more analytes and test subjects and a simulated transport time for plasma, because of the increased risk for hemolysis, to confirm if the same setting can be used for microtainer tubes (899g) as for the older microtainer tube and vacutainer tube (1300g).

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders and it is caused by a loss of dopamine (DA) producing neurons in the basal ganglia in the brain. The PD patient suffers from motor symptoms such as tremor, bradykinesia and rigidity and treatment with levodopa (LD), the precursor of DA, has positive effects on these symptoms. Several factors affect the availability of orally given LD. Gastric emptying (GE) is one factor and it has been shown to be delayed in PD patients resulting in impaired levodopa uptake. Different enzymes metabolize LD on its way from the gut to the brain resulting in less LD available in the brain and more side effects from the metabolites. By adding dopa decarboxylase inhibitors (carbidopa or benserazide) or COMT-inhibitors (e.g. entacapone) the bioavailability of LD increases significantly and more LD can pass the blood-brain-barrier and be converted to DA in the brain. It has been considered of importance to avoid high levodopa peaks in the brain because this seems to induce changes in postsynaptic dopaminergic neurons causing disabling motor complications in PD patients. More continuously given LD, e.g. duodenal or intravenous (IV) infusions, has been shown to improve these motor complications. Deep brain stimulation of the subthalamic nucleus (STN DBS) has also been proven to improve motor complications and to make it possible to reduce the LD dosage in PD patients. In this doctoral thesis the main purpose is to study the pharmacokinetics of LD in patients with PD and motor complications; in blood and subcutaneous tissue and study the effect of GE and PD stage on LD uptake and the effect of continuously given LD (CDS) on LD uptake and GE; in blood and cerebrospinal fluid (CSF) when adding the peripheral enzyme inhibitors entacapone and carbidopa to LD infusion IV; in brain during STN DBSand during oral or IV LD treatment. To conclude, LD uptake is more favorable in PD patients with less severe disease and GE is delayed in PD patients. No obvious relation between LD uptake and GE or between GE and PD stage is seen and CDS decreases the LD levels. Entacapone increases the maximal concentration of LD in blood and CSF. This is more evident with additional carbidopa and important to consider in avoiding high LD peaks in brain during PD treatment. LD in brain increases during both oral and IV LD treatment and the DA levels follows LD well indicating that PD patients still have capacity to metabolize LD to DA despite probable pronounced nigral degeneration. STN DBS seems to increase putaminal DA levels and together with IV LD treatment also increases LD in brain possibly explaining why it is possible to decrease LD medication after STN DBS surgery. / Parkinsons sjukdom (PS) är en av de vanligaste s.k. neurodegenerativasjukdomarna och orsakas av förlust av dopamin(DA)producerande nervceller i hjärnan. Detta orsakar motoriska symptom såsom skakningar, stelhet och förlångsammade rörelser. Levodopa (LD) är ett ämne, som kan omvandlas till DA i hjärnan och ge symptomlindring och det är oftast förstahandsval vid behandling av patienter med PS. Flera faktorer påverkar tillgängligheten av LD, bl.a. den hastighet som magsäcken tömmer sig med och denna verkar förlångsammad hos personer med PS vilket ger sämre tillgänglighet av LD i blodet och därmed i hjärnan. LD bryts även ner i hög grad av olika enzym ute i kroppen vilket leder till mindre mängd LD som hamnar i hjärnan och till fler nedbrytningsprodukter som orsakar biverkningar. Tillägg av enzymhämmare leder till ökad mängd LD som kan nå hjärnan och omvandlas till DA. Det anses viktigt att undvika höga toppar av LD i hjärnan då dessa verkar bidra till utvecklandet av besvärliga motoriska komplikationer hos patienter med PS. Om LD ges mer kontinuerligt, exempelvis som en kontinuerlig infusion in i tarmen eller i blodet, så minskar dessa motoriska komplikationer. Inopererande av stimulatorer i vissa delar av hjärnan (DBS) har också visat sig minska dessa motoriska komplikationer och även resultera i att man kan minska LD-dosen. Huvudsyftet med den här avhandlingen är att studera LD hos patienter med PS; i blod och fettvävnad då LD ges i tablettform och se om det finns något samband med LD-upptag och hastigheten på magsäckstömningen (MT) och om kontinuerligt given LD påverkar LD-upptaget eller MT; i blod och i ryggmärgsvätska då enzymhämmarna entakapon och karbidopa tillsätts LD; i hjärna vid behandling med DBS och då LD ges både som tablett och som infusion i blodet. Sammanfattningsvis kan vi se att LD-upptaget är mer gynnsamt hos patienter med PS i tidigare skede av sjukdomens komplikationsfas. MT är förlångsammad hos patienter med PS och det är inget tydligt samband mellan LD-upptag och MT eller mellan MT och sjukdomsgrad. Kontinuerligt given LD minskar LDnivåerna. Enzymhämmaren entakapon ökar den maximala koncentrationen av LD i blod och ryggmärgsvätska och effekten är mer tydlig vid tillägg av karbidopa vilket är viktigt att ta i beaktande vid behandling av PS för att undvika höga toppar av LD i hjärnan. LD ökar i hjärnan då man behandlar med LD i tablettform och som infusion i blodet och DA-nivåerna i hjärnan följer LD väl vilket visar på att patienter med PS fortfarande kan omvandla LD till DA trots trolig uttalad brist av de DA-producerande nervcellerna i hjärnan. DBS verkar öka DA i vissa områden i hjärnan och tillsammans med LD-infusion i blodet verkar det även öka LD i hjärnan och det kan förklara varför man kan sänka LDdosen efter DBS-operation.

Alcohol use disorder (AUD) is a complex disorder with multiple pathophysiological processes contributing to the initiation, progression and development of the disease state. AUD is a chronic relapsing disease with escalation of alcohol-intake over time in repeated cycles of tolerance, abstinence and relapse and hence, it is very difficult to treat. There are only a few currently available treatments with narrow efficacy and variable patient response. Thus it is important to find new, more effective medications to increase the number of patients who can benefit from pharmacological treatment of AUD. The research presented in this thesis work focuses on the critical involvement of central neuropeptides in alcohol-related behaviors. The overall aim was to evaluate the nociceptin/orphanin FQ (NOP) receptor, the neuropeptide Y (NPY) Y2 receptor and the melanin-concentrating hormone (MCH) receptor 1 as novel and potential pharmacological treatment targets for AUD by testing the NOP receptor agonist SR-8993, the NPY-Y2 receptor antagonist CYM-9840 and the MCH1 receptor antagonist GW803430 in established animal models. In the first study (Paper I), the novel and selective NOP agonist SR-8993 was assessed in rat models of motivation to obtain alcohol and relapse to alcohol seeking behavior using the operant self-administration (SA) paradigm. Firstly, treatment with SR-8993 (1 mg/kg) showed a mildly anxiolytic effect and reversed acute alcohol withdrawal-induced “hangover” anxiety in the elevated plus-maze (EPM). Next, it potently attenuated alcohol SA and motivation to obtain alcohol in the progressive ratio responding (PRR) and reduced both alcohol cue-induced and yohimbine stress-induced reinstatement of alcohol seeking, without affecting the pharmacology and metabolism of alcohol nor other control behaviors. To extend these findings, SR-8993 was evaluated in escalated alcohol-intake in rats.  Treatment with SR-8993 significantly suppressed alcohol-intake and preference in rats that were trained to consume high amounts of alcohol in the two-bottle free choice intermittent access (IA) paradigm. SR-8993 also blocked operant SA of alcohol in rats that showed robust escalation in operant alcohol SA following chronic IA exposure to alcohol. In the second study (Paper II), SR-8993 was further evaluated in a model for escalated alcohol-intake induced by long-term IA exposure to alcohol. The effect of previous experience on operant alcohol SA on two-bottle free choice preference drinking was evaluated and sensitivity to treatment with SR-8993 was tested in rats selected for escalated and non-escalated alcohol seeking behavior. We found that rats exposed to the combined SA-IA paradigm showed greater sensitivity to SR-8993 treatment. In addition, acute escalation of alcohol SA after a three-week period of abstinence was completely abolished by pretreatment with SR-8993. In the third study (Paper III), the effects of the novel, small molecule NPY-Y2 antagonist CYM-9840 were tested in operant alcohol SA, PRR which is a model for motivation to work for alcohol and reinstatement of alcohol-seeking behavior. Treatment with CYM-9840 (10 mg/kg) potently attenuated alcohol SA, progressive ratio responding and stress-induced reinstatement using yohimbine as the stressor, while alcohol cue-induced reinstatement was unaffected. Moreover, a range of control behaviors including taste sensitivity, locomotor and pharmacological sensitivity to the sedative effects of alcohol remained unaffected by CYM-9840 pretreatment, indicating that its effects are specific to the rewarding and motivational aspects of alcohol-intake and related behaviors. CYM-9840 also reversed acute alcohol withdrawal-induced “hangover” anxiety measured in the EPM and reduced alcohol-intake in the 4 hour limited access two-bottle free choice preference drinking model. Finally, in the fourth study (Paper IV), the selective MCH1-R antagonist GW803430 was tested in rat models of escalated alcohol-intake. Pretreatment with GW803430 (effective at 10 &amp; 30 mg/kg) dose-dependently reduced alcohol and food-intake in rats that consumed high amounts of alcohol during IA, while it only decreased food-intake in rats that consumed low amounts of alcohol during IA, likely due to a floor effect. Upon protracted abstinence following IA, GW803430 significantly reduced operant alcohol SA and this was associated with adaptations in MCH and MCH1-R gene-expression. In contrast, GW803430 did not affect escalated alcohol SA induced by chronic alcohol vapor exposure and this was accompanied by no change in MCH or MCH1-R gene expression. Overall, these results suggest that the MCH1-R antagonist affects alcohol-intake through regulation of both motivation for caloric-intake and the rewarding properties of alcohol. In conclusion, our results suggest critical roles for these central neuropeptides in the regulation of anxiety and of alcohol reward, making them potential pharmacological targets in the treatment of AUD.

Background Many risk factors for stroke are well characterized and might, at least to some extent, be similar for first-ever stroke and for recurrent stroke events. However, previous studies have shown heterogeneous results on predictors and rates of stroke recurrence. Patients who survive spontaneous intracerebral hemorrhage (ICH) often have compelling indications for antithrombotic (AT) treatment (antiplatelet (AP) and/or anticoagulant (AC) treatment), but due to controversy of the decision to treat, a large proportion of these patients are untreated. In the absence of evidence from randomized controlled trials (RCTs), there is need for more high- quality observational data on the clinical impact of, and optimal timing of AT in ICH survivors. The aims of this thesis were to assess time trends in stroke recurrence, to determine the factors associated with an increased risk of stroke recurrence – including socioeconomic factors – and to determine to what extent ICH survivors with and without atrial fibrillation (AF) receive AT treatment and to determine the optimal timing (if any) of such treatment.  Methods The population-based Monitoring Trends and Determinants of Cardiovascular Disease (MONICA) stroke incidence register was used to assess the epidemiology and predictors of stroke recurrence after ischemic stroke (IS) and ICH from 1995 to 2008 in northern Sweden. Riksstroke, the Swedish stroke register, linked with the National Patient Register and the Swedish Dispensed Drug Register, made it possible to identify survivors of first-ever ICH from 2005 to 2012 with and without concomitant AF to investigate to what extent these patients were prescribed AP and AC therapy. The optimal timing of initiating treatment following ICH in patients with AF 2005–2012 was described through separate cumulative incidence functions for severe thrombotic and hemorrhagic events and for the combined endpoint “vascular death or non-fatal stroke”. Riksstroke data on first-ever stroke patients from 2001 to 2012 was linked to the Longitudinal Integration Database for Health Insurance and Labour market studies to add information on education and income to investigate the relationship between socioeconomic status and risk of recurrence. Results Comparison between the cohorts of 1995–1998 and 2004–2008 showed declining risk of stroke recurrence (hazard ratio: 0.64, 95% confidence interval (CI): 0.52-0.78) in northern Sweden. Significant factors associated with an increased risk of stroke recurrence were age and diabetes. Following ICH, a majority (62%) of recurrent stroke events were ischemic.  The nationwide Riksstroke study confirmed the declining incidence, and it further concluded that low income, primary school as highest attained level of education, and living alone were associated with a higher risk of recurrence beyond the acute phase. The inverse effects of socioeconomic status on risk of recurrence did not differ between men and women and persisted over the study period. Of Swedish ICH-survivors with AF, 8.5% were prescribed AC and 36.6% AP treatment, within 6 months of ICH. In patients with AF, predictors of AC treatment were less severe ICH, younger age, previous anticoagulation, valvular disease and previous IS. High CHA2DS2-VASc scores did not seem to correlate with AC treatment. We observed both an increasing proportion of AC treatment at time of the initial ICH (8.1% in 2006 compared with 14.6% in 2012) and a secular trend of increasing AC use one year after discharge (8.3% in 2006 versus 17.2% in 2011) (p&lt;0.001 assuming linear trends). In patients with high cardiovascular event risk, AC treatment was associated with a reduced risk of vascular death and non-fatal stroke with no significantly increased risk of severe hemorrhage. The benefit appeared to be greatest when treatment was started 7–8 weeks after ICH. For high-risk women, the total risk of vascular death or stroke recurrence within three years was 17.0% when AC treatment was initiated eight weeks after ICH and 28.6% without any antithrombotic treatment (95% CI for difference: 1.4% to 21.8%). For high-risk men, the corresponding risks were 14.3% vs. 23.6% (95% CI for difference: 0.4% to 18.2%). Conclusion Stroke recurrence is declining in Sweden, but it is still common among stroke survivors and has a severe impact on patient morbidity and mortality. Age, diabetes and low socioeconomic status are predictors of stroke recurrence. Regarding ICH survivors with concomitant AF, physicians face the clinical dilemma of balancing the risks of thrombosis and bleeding. In awaiting evidence from RCTs, our results show that AC treatment in ICH survivors with AF was initiated more frequently over the study period, which seems beneficial, particularly in high-risk patients. The optimal timing of anticoagulation following ICH in AF patients seems to be around 7–8 weeks following the hemorrhage.

Background: The risk of ischaemic stroke in patients with atrial fibrillation (AF) and mechanical heart valve (MHV) prostheses can be reduced by oral anticoagulation (OAC), which increases the risk of serious bleeding. The aims of this thesis were [1] to find out how effective and safe warfarin is where treatment quality is high, i.e. Sweden, with proportion of time that patients spend within the therapeutic range (TTR) &gt;70%, [2] whether there is evidence for administering low-molecular-weight heparin (LMWH) during temporary interruptions of OAC (bridging therapy), and whether non-vitamin K-dependent oral anticoagulants (NOACs) as a group, [3] or individually, [4] are more effective and safer than warfarin when used for stroke prevention in patients with AF. Materials and methods: All four studies were retrospective, based on the Swedish anticoagulation register Auricula, and done with merging of data from some or all of the National Patient Register, the Prescribed Drug Register, the Swedish Stroke Register (Riksstroke), and the Cause of Death Register. In studies 2–4, propensity score matching was performed to obtain treatment groups with similar risk profiles. Outcomes were defined as haemorrhages or thromboses requiring specialist care, or death. Haemorrhages were intracranial, gastrointestinal, or other. Thromboses were ischaemic stroke, systemic embolism, myocardial infarction, or venous thromboembolism (VTE). Study 1 described all patients on warfarin during 2006–2011, which was before the introduction of NOACs. Study 2 was a cohort study of all patients who had a planned interruption of warfarin during the same period. Study 3 included all 49,011 patients starting OAC for stroke prevention due to AF between 1 July 2011 and 31 December 2014, and study 4 all 64,382 patients with the same indication between 1 January 2013 and 31 December 2015. Results: Study 1 showed that for the 77,423 patients on warfarin with 217,804 treatment years, TTR was 77.4% for patients with AF, 74.5% with MHV, and 75.9% with VTE. Annual rates of intracranial bleeding were 0.38%, 0.51%, and 0.30%. In study 2, with 14,556 warfarin interruptions, the 30-day risk of a bleeding requiring specialist care was 0.64% for LMWH treated and 0.46% for controls. For patients with VTE as indication for OAC, bleeding rate with LMWH was significantly higher at 0.85% vs. 0.16% (hazard ratio 5.24, 95% confidence interval 1.39–19.77), but with no difference for patients with MHV or AF. The incidence of ischaemic complications was higher in the LMWH bridging group overall and for patients with MHV and AF, but not for patients with VTE. In study 3, for the 12,694 patients starting NOAC (10,392 treatment years) or matched warfarin patients (9,835 treatment years, TTR 70%) due to AF, annual incidence of ischaemic stroke and systemic embolism did not differ between the groups (1.35% vs. 1.58%), but risks of major bleedings and intracranial bleedings were significantly lower: 2.76% vs. 3.61% and 0.40% vs. 0.69%. In study 4, patients on individual NOACs (6,574 dabigatran, 8,323 rivaroxaban, 12,311 apixaban) were compared to 37,174 patients starting warfarin (in total 81,176 treatment years). No NOAC showed any difference in risk of ischaemic stroke or systemic embolism, but there were fewer intracranial bleedings, serious bleedings overall, and deaths for dabigatran and apixaban compared to warfarin. For patients starting rivaroxaban the risk of gastrointestinal bleeding was higher than for matched warfarin counterparts, with no significant differences in other bleeding risks, or mortality. Conclusions: Swedish warfarin treatment shows TTR levels that are high by international standards, correlating to low incidences of ischaemic and haemorrhagic events. LMWH bridging has not been proven beneficial, even for patients with MHV, meaning that bridging in general cannot be recommended. NOACs as a group were safer than high-quality warfarin treatment. Efficacy did not differ, even when comparing individual NOACs to warfarin, but there were fewer bleedings on dabigatran and apixaban. Although not more efficient than warfarin with a high TTR, NOACs should be the recommended first choice for OAC in AF, on the merit of lower bleeding risks. / <p>Finansiär: Forskning och Utveckling, Region Västernorrland</p>

Intensivvård är en avancerad och resurskrävande form av vård och ställer stora krav på intensivvårdssjuksköterskans kompetens och kunskapsnivå. Tidigare studier inom området belyser i huvudsak den grundutbildade sjuksköterskans upplevelser av att vara ny på en intensivvårdsavdelning och deras erfarenheter av introduktionen. Däremot saknas kunskap som beskriver den nyutbildade IVA-sjuksköterskans upplevelser av att vara ny på en intensivvårdsavdelning samt deras erfarenheter av given introduktion. Syftet med studien var att beskriva nyutbildade intensivvårdssjuksköterskors upplevelser av att vara ny på en intensivvårdsavdelning samt belysa deras erfarenheter av given introduktion. Datamaterialet bestod av beskrivande berättelser som analyserades enligt kvalitativ innehållsanalys med en induktiv ansats. I resultatet framkom tre kategorier; ”Från osäkerhet till ansvarskännande”, ”Stöd under introduktionen gav trygghet” och ”Brist på tid, uppföljning och kontinuitet av handledare under introduktionen upplevdes otryggt”. Deltagarna upplevde en osäkerhet i sin nya roll som IVA-sjuksköterska kopplat till bristande klinisk kunskap och erfarenhet. Stödet de fick under introduktionen av en checklista, kollegor, handledare och mentorer gav trygghet. Brist på tid för handledning samt bristande uppföljning och kontinuitet av handledare under introduktionen upplevdes otryggt och negativt för utvecklingen som novis. Konklusionen av resultatet var att IVA-sjuksköterskan upplevde en osäkerhet i början av sin anställning vid intensivvårdsavdelningen men med en stöttande i / Intensive care is the most advanced and resourcing care and demands great competence and level of knowledge on the intensive care nurse. Previous research shows newly trained nurses experiences of starting to work in an intensive care unit and their experiences of the introduction. While there is a lack of knowledge that describes newly trained ICU-nurses experiences of being new in an intensive care unit and their experiences of the given introduction. The aim of this study was to describe newly trained ICU-nurses experiences of being new in an intensive care unit and their experiences of the given introduction. The data consisted of descriptive stories that were analyzed according to qualitative content analysis with an inductive approach. The result shows three categories; "From uncertainty to a sense of responsibility", "Support during the introduction gave sense of security" and "Lack of time, follow-up and continuity of supervisors during the introduction was experienced uncertain”. The participants experienced an uncertainty in their new role as an ICU-nurse linked to a lack of clinical knowledge and experience. The support they received during the introduction of a checklist, colleagues, supervisors and mentors provided security. Lack of time for supervision and lack of follow-up and continuity of supervisors during the introduction was perceived as insecure and negative for the progress as a novice. The conclusion of the result was that the ICU-nurses experienced insecurity in the beginning but with a supportive introduction the feeling of being a novice nurse became a feeling of being an advanced beginner.

The global population with dementia is rapidly increasing around the world.The major risk factor for dementia is aging. There is currently no treatmentavailable and the cost of symptomatic treatment is high. There is a growinginterest in possible clinical applications of non-invasive methods that are safeand easy-to-perform in diagnosis of dementia. The purpose of this paper is toinvestigate the usage of transcranial magnetic stimulation (TMS) withelectroencephalography (EEG) to diagnose dementia in early stages of thedisease. Early diagnosis is needed to reduce the costs of symptomatic care.When investigating the usage of TMS-EEG technology, we will look at how wecan distinguish dementia in different neurodegenerative diseases between eachother. More research is needed to suggest an accurate parameters fordiagnosis of dementia with this type of technology.

Psychiatry is in a crisis. Mental health disorders are on the rise worldwide and there are currently not enough efficient treatment methods that would meet the patients’ needs. Hence, the societal and economic costs of mental health problems are enormous, as well as the suffering of individuals afflicted by mental health problems. Lysergic acid diethylamide (LSD) and psilocybin are substances that create an altered state of consciousness characterized by altered sensory perception and on some occasions, ego-dissolution, and mystical experiences. In recent studies, LSD and psilocybin have been shown to carry significant therapeutic potential in the treatment of depression and anxiety disorders in conjunction with psychotherapy. The therapeutic effects of LSD and psilocybin have also been shown to persist for between 3-12 months post-treatment. LSD and psilocybin, like other classical hallucinogens, increase serotonin availability, which has been suggested to attenuate symptoms of anxiety and depression. In addition, LSD and psilocybin alter the activity of the default mode network, which has been suggested to be overly active in depressed and anxious patients. This essay is a literature review of the neural mechanisms of LSD and psilocybin, their potential therapeutic effects in the treatment of depressive and anxiety disorders, and how insights about said neural mechanisms may be useful in understanding the possible application of psychedelics in the treatment of depressive and anxiety disorders. In sum, recent studies have provided converging and convincing evidence on therapeutic potential of LSD and psilocybin. Yet, few conclusions on the exact neural mechanisms of how LSD and psilocybin alleviate depressive and anxiety symptoms can be made. Although the future of this research field looks promising, archaic national- and international regulations continue to be a hindrance to research into psychedelic drugs. Yet, due to the psychiatric crisis and the promising results so far, more studies in this field are warranted.

This thesis presents a real time software program written in MATLAB using off-the-self MEMS sensors from Shimmer-Research®. Parallel to the software development, a proof of concept was conducted using the produced program to quantify stride length, stride length variance and stride time for patients diagnosed with Parkinson's disease. Results from testing showed that the system measured the mean stride length error to 2.4% of stride length and a standard deviation of 13.7% of stride length. Results from testing further showed a stride time error of 2.70% of individual stride times with a standard deviation of 1.89%. The system shows promise as a pedagogical, gait analysis training tool for physiotherapists as well as in academic teaching. The system is flexible and data processing functions can be readily re-programmed with other or additional processing features while maintaining user feedback, storage and plotting functionalities implemented in the current version of the program.