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Periodontitis and coronary artery disease (CAD) are highly prevalent in Sweden’s population; both diseases have complicated pathogeneses and clinical manifestations due to immune-system triggered inflammation. Research in recent years reported that inflammation is a significant active participant in many chronic diseases. The literature described a CAD-periodontitis association, but underlying mechanisms are not fully understood. It is important to acquire knowledge about how periodontitis might influence CAD, which is one of the major causes of illness and death in western countries. Because periodontitis can be treated, this knowledge, when complemented with more knowledge about the CAD-periodontitis association, could lead to CAD prevention. The overall aim of studies reported in this thesis were to investigate the CAD-periodontitis association, and specifically, to: (i) compare periodontal conditions in patients with CAD and subjects without a history of CAD; (ii) study whether or not periodontal status influences outcomes in known CAD over an 8-year period; (iii) study whether or not concentrations and biological activity of hepatocyte growth factor (HGF) in serum from patients with severe CAD are different – depending on whether or not the subjects had periodontitis; and (iv) study concentrations and biological activity of hepatocyte growth factor in serum, saliva, and gingival crevicular fluid in healthy subjects with or without periodontitis. Here is a brief summary: In study I, 161 patients with CAD and 162 controls were compared regarding periodontal disease prevalence and severity. CAD patients had significant coronary stenosis and underwent percutaneous coronary intervention (PCI) or coronary artery by-pass grafts (CABG). Healthy controls were recruited from Sweden’s population database. Twenty-five per cent of the CAD patients had severe periodontitis, compared to 8% of the controls. In a multiple logistic regression analysis (controlled for age and smoking), severe periodontitis indicated an odds ratio of 5.74 (2.07–15.90) for CAD. Study II: Periodontal status was re-examined in 126 CAD patients and 121 controls from the initial sample after 8 years. Periodontal status at baseline was analysed and related to CAD endpoints (i.e., myocardial infarction, new PCI or CABG or death due to CAD) recorded from patients’ medical records and from the death index maintained by the National Board of Health and Welfare. The difference in periodontitis prevalence and severity between the two groups remained unchanged during the 8-year follow up. No significant differences were found regarding CAD endpoints during follow-up in relation to baseline periodontal status in the CAD-patient group. In study III, higher HGF serum concentrations (p&lt;0.001) were found in CAD patients, compared to healthy blood donors, which reflects chronic inflammation. In CAD patients without periodontitis, HGF concentrations increased significantly 24 hours after PCI – in parallel with increased HGF biological activity. In CAD patients with periodontitis, only small fluctuations were seen in HGF values, i.e., concentration and biological activity. HGF biological activity was temporarily elevated after PCI but only in patients without periodontitis. Thus chronic inflammation related to periodontitis might reduce HGF biological activity. In study IV, HGF concentration and biological activity in saliva, in gingival crevicular fluid (GCF), and serum were compared between 30 generally healthy subjects with severe untreated periodontitis and 30 healthy subjects without periodontitis. Compared to periodontally healthy controls, periodontal patients showed higher HGF concentrations in saliva p&lt;0.001, gingival crevicular fluid p&lt;0.0001, and in serum p&lt;0.001. HGF biological activity (measured as the binding affinity to its HSPG and c-MET receptors) was significantly reduced in saliva (p&lt;0.0001) and GCF samples (p&lt;0.0001 for HSPG and p&lt;0.01 for c-MET) from periodontitis patients. The only significant difference in serum samples was an increases in c-MET binding three minutes after subgingival debridement in periodontitis patients (p&lt;0.05), which might reflect that patients had active bursts of periodontitis. In conclusion, CAD patients more often showed severe periodontitis but there were no differences in CAD endpoints during the eight-year follow-up in relation to baseline periodontal status. Periodontitis seems to influence HGF concentration and biological activity in CAD patients, but studies on factors that cause lower HGF biological activity are necessary – to find out if periodontal treatment influences HGF biological activity. Healthy periodontitis patients had higher HGF concentrations locally and systemically, but biological activity was reduced. This might indicate that periodontitis can influence wound healing and tissue repair in other body parts. / <p>The ISBN 987‐91‐7519‐748‐7 is incorrect. Correct ISBN is 978‐91‐7519‐748‐7.</p>

Parkinson’s disease (PD) is a neurodegenerative disease affecting approximately 25000 people in Sweden. The main cause of the disease is the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc) projecting to the striatum. The motor symptoms of PD, due to decreased levels of dopamine, includes bradykinesia, rigidity and tremor. During the 1960ies oral L-dopa treatment was introduced increasing quality of life for PD patients. In recent decades, enzyme inhibitors have been introduced, increasing bioavailability of L-dopa in plasma. After 5-10 years of L-dopa treatment, 50% of PD patients develop disabling dyskinesias. This can be due to rapid changes in L-dopa conentrations with non physiological stimulation of the dopamine receptor. For over 20 years deep brain stimulation (DBS) has grown to be a good neurosurgical procedure for improving quality of life in advanced PD with disabling dyskinesias. With stereotactic technique, electrodes are implanted in the brain and connected to a pacemaker sending electrical impulses. The most common target in PD is the subthalamic nucleus (STN). The knowledge about DBS mechanism(s) and its interaction with L-dopa is unsatisfactory. The aims of this thesis were; to study the effect of the enzyme inhibitor entacapone on the L-dopa concentration over the blood brain barrier (BBB); to study possible interactions between L-dopa and DBS; to study alterations in neurotransmitters during DBS; to visualize microdialysis catheters in anatomical targets and to estimate sampling area of the catheters. In all four papers the microdialysis technique was used. It is a well-established technique for continuous sampling of small water-soluble molecules within the extracellular fluid space in vivo, allowing studies of pharmaceutical drugs and neurotransmitters. We showed that entacapone increases the bioavailability of L-dopa in blood with a subsequent increase of L-dopa peak levels in the cerebrospinal fluid. This in turn may cause a larger burden on the dopaminergic neurons causing an increased degeneration rate and worsening of the dyskinesias; we showed that 18% of L-dopa crosses the BBB and that there is a possible interaction between L-dopa and DBS, L-dopa concentrations increase during concomitant STN DBS, which can clarify why its possible to decrease L-dopa medication after DBS surgery. The research has also shown that STN DBS has an effect on various neurotransmitter systems, mainly L-dopa, dopamine and GABA. We showed that STN DBS may have an effect on the SNc, resulting in putaminal dopamine release. We have shown that with stereotactic technique, it is safe to do microdialysis sampling in specific areas in the human brain. Simulations with the finite element method combined with patient specific preoperative MRI and postoperative CT images gave us exact knowledge about the positions of the catheters and that the studied structures were the intended. The research has given an assumption of the maximum tissue volume that can be sampled around the microdialysis catheters.

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Syfte Syftet med denna studie var att undersöka om användningen av sociala medier medför en ökad risk för psykisk ohälsa hos pojkar och flickor i årskurs 9. Vi hade en hypotes att sociala medier leder till en ökad risk för psykisk ohälsa främst hos flickor. Med hjälp av vår enkät hade vi som mål att besvara tre frågeställningar: Hur ser användningen av sociala medier ut hos ungdomarna? På vilket sätt påverkas ungdomarna av sociala medier gällande kroppsideal? Finns det ett samband mellan användning av sociala medier och psykisk ohälsa oberoende av sömn, sociala förhållanden, relationer och kost? Metod Totalt deltog 69 elever, varav 32 flickor och 37 pojkar i åldrarna 15-16 år. Vi använde en kvantitativ metod i form av enkäter. Tanken med detta metodval var att vi under kort tid skulle kunna få ett relativt stort urval att besvara våra frågeställningar. Enkäten var utformad med 32 frågor, vissa med kryssfrågor och andra med fritext, dessa delades ut till två skolor i Solna. Analys av resultaten genomfördes med hjälp av programvaran SPSS. Oparat t-test användes för att analysera om det fanns någon signifikant skillnad mellan könen (signifikantnivån var satt till p &lt; 0,05). Linjär regressionsanalys genomfördes för att undersöka om psykisk ohälsa har ett samband med sociala medier. Resultat Resultaten visade att sociala mediers bidrag till psykisk ohälsa endast utgjorde 3 %. Det var mer tydligt att majoriteten av andra påverkansfaktorer så kallade ko-variater oberoende av varandra hade större bidragande roll vad gäller risken att drabbas av psykisk ohälsa, än vad sociala medier hade. Okända faktorer som inte studerades utgjorde 66 % av den ökade risken för psykisk ohälsa. Gällande utseende kopplat till sociala medier uppgav 19 % av flickorna och 5 % av pojkarna att de känner sig missnöjda. Detta gav en signifikant skillnad mellan könen. Slutsats Utifrån resultaten drogs slutsatsen att det inte fanns någon koppling mellan risken för att psykisk ohälsa ökar i samband med användning av sociala medier samt att ingen signifikant skillnad finns mellan könen.

Introduktion: Klassifikationssystemet i FASS har sedan 1970-talet genomförts för att klassificera läkemedel vad gäller risk under graviditet och amning. Efter talidomidkatastrofen på 1960-talet, började många företag varna för sina läkemedelsprodukter. Framförallt varnade man för de produkter som saknade utförda kliniska studier eller studier på djur som visade sig vara riskfria att användas under graviditet. Sedan klassifikationssystemet inträdde har man varit kritisk mot det. Kritiken har varit emot de förklaringar som finns till de olika kategorierna eftersom man ansett att de är svårförståeliga för både förskrivare, exempelvis läkare, och patienter. Syfte: Granska ATC-gruppen C10AA(HMG-CoA-reduktashämmare) gällande risk under graviditet för att undersöka hur trovärdig och professionell FASS-texten är. Material och Metod: En granskning av graviditetsavsnittet i FASS.se för 81 produkter. Resultat: 28 produkter behövde en omjustering, 32 produkter både en omjustering och omklassificering av graviditets-kategorin och 11 produkter utan anmärkning. Slutsats: av detta arbete kan man säga att klassifikationssystemet som finns idag i FASS är viktigt och bra att det finns som hjälp för alla förskrivare och andra sjukvårdspersonal för att kunna välja rätt och säker behandling. Texterna som läggs upp i FASS behöver kontrolleras mer. Därmed behöver man en grupp som kontrollerar alla texter innan dessa finns tillgängliga i FASS. Gruppen ska exempelvis lägga till information som är aktuell och ta bort sådan information som vid det tillfället är inaktuell.

Background and Aim: In 2010 HPV vaccination was subsidized in Sweden and in 2012 a national vaccination program against HPV16, 18, 6 and 11 was launched for girls ages 10-12 years. In parallel was a catch-up vaccination program for young women. To investigate base line HPV cervical and oral prevalence in non-vaccinated youth two studies were performed at a youth clinic in Stockholm 2008-2011. This project initiated 2013 aimed to follow HPV prevalence in youth since the previous studies, in the same population.   Materials and Methods: 117 women, of which 73% were HPV catch-up vaccinated donated 93 cervical samples and 117 oral samples, and 54 unvaccinated men donated 54 oral samples and 47 urinary samples. All samples were tested for 27 HPV types with a PCR based system and the data was compared to that obtained in 2008-2011. The categorical Fishers exact test was used for statistical analysis due to HPV-positive samples being n&lt; 5 for certain types.  Results and Conclusion: HPV16 cervical prevalence was significantly lower in the HPV vaccinated women compared to unvaccinated women (7% and 27% respectively, p=0.033) in the 2013 group. For HPV18 and HPV6 there was a significantly lower prevalence in the 2013 vaccinated group compared to the 2008-2010 unvaccinated group (1.5% vs. 10% respectively, p=0.021 and 1.5% vs. 8% respectively, p=0.048). Overall oral HPV prevalence for both genders, was lower in the 2013 group compared to that of 2009-2011, (2.3% and 9.1% respectively, p=0.005). Male urinary prevalence was low (6%) and not efficient to follow changes in specific HPV types. The data indicate that HPV catch-up vaccination was gradually exhibiting an effect, with significant decrease of cervical HPV16 prevalence.

Sveriges befolkning blir allt äldre och med ökande ålder ökar riskerna för att drabbas av sjukdomar som kräver behandling. Fysiologiska förändringar och multimedicinering ökar riskerna för läkemedelsrelaterade problem. Med hjälp av läkemedelsgenomgångar kan läkemedelsrelaterade problem upptäckas, åtgärdas och förebyggas vilket ökar säkerheten och kvalitén i läkemedelsbehandlingen. Inom vården genomförs läkemedelsgenomgångarna främst av läkare. Dock kan farmaceutens expertis i vårdteamet ge ytterligare fördelar med avseende på lägre läkemedelskostnader och bättre livskvalité hos patienterna. Syftet med arbetet var att undersöka effekterna av farmaceutiska läkemedelsgenomgångar på multi-medicinerade äldre patienter. Arbetet var en litteraturstudie där totalt fem studier från databasen PubMed granskades. Tre av studierna genomförde farmaceutiska läkemedels-genomgångar på äldre multimedicinerade patienter på apotek medan två av studierna genomförde dem inom primärvården. Läkemedelsgenomgångarna resulterade i 1,2 till 4,1 funna läkemedelsrelaterade problem/patient. De vanligaste problemen var ’överbehandling’, ’bristande följsamhet’, ’utgången indikation’, ’onödig medicinering’ och ’läkemedels-biverkningar’. Den vanligaste interventionen farmaceuten föreslog i studierna var att stoppa behandlingen. Genomförda interventioner rapporterades i fyra av studierna med varierande genomförandegrad, från 3,9% till 56%. I två av studierna redovisades en minskning av läkemedelsrelaterade problem hos patienterna, från 4,1 till 3,3 läkemedelsrelaterade problem/patient och från 1,7 till 1,3 läkemedelsrelaterade problem/patient. Analyserna av studierna visar att farmaceutiska läkemedelsgenomgångar på apotek och inom öppenvård kan reducera antalet läkemedelsrelaterade problem. Alla studier visade inte resultat på antalet läkemedelsrelaterade problem/patient efter farmaceutens föreslagna intervention. Dock kan resultaten från genomförda interventioner ändå tyda på att farmaceutiska läkemedels-genomgångar har en effekt för multimedicinerade patienter. Det krävs mer kunskap i hur äldre patienter ska behandlas samt ett bra samarbete mellan vården och apoteken för att de läkemedelsrelaterade problem ska bli färre. / The population of elderly people in Sweden is increasing and old patient have higher risk of suffering from diseases that require treatment. Physiological changes and multi-medication increase the risk of drug-related problems. The medication reviews can detect, correct and prevent drug-related problems which will improve the safety and quality in the drug treatment. Medication reviews are mainly conducted by physicians in health care. However, with the expertise of pharmacists as a part of the health care team, benefits such as lower drug costs and better quality of life can be seen. The aim of this study was to investigate the effects of pharmacist-led medication review at multi-medicated elderly patient. This study was a literature study and the articles were collected from PubMed. A total of five studies were reviewed. The pharmacutical medication review of the multi-medicated elderly people were conducted at community pharmacies in Netherlands and Schwitzerland in three of the studies and two of them were conducted within the Swedish primary health care. The results from the pharmacutical medical reviews revealed 1,2 to 4,1 drug-related problems/patient. The most common problems were ’over-treatment, ’non-compliance’, ’expired indication’, ’unnecessary therapy’ and ’adverse drug effect’. The most common intervention the pharmacist suggested, in all of the studies, was to stop the treatment. Implemented interventions were reported in varying implementation rate in four of the studies, from 3,9% to 56%. Two of the studies reported a reduction of drug-related problems/patient. From 4,1 to 3,3 drug-related problems/patient and from 1,7 to 1,3 drug-related problems/patient. The analyzes of the studies show that pharmacist-led medication reviews at community pharmacies and in the primary health care can reduce the number of drug-related problems. Not all of the studies presented results of drug-related problem/patient after the pharmacist´s proposed intervention. However, the results of implemented interventions indicate that pharmaceutical medication reviews have a positive effect for multi-medicated patients. In order to decrease the number of drug-related problems in elderly patients, more knowledge with regard to pharmaceutical treatment of elderly as well as better cooperation between helthcare and pharmacies is required.