Background: Tablets are the most common form of medication due to the simplicity and relatively cheap price in manufacturing them and also due to the easy administration method. Not all drug substances are available in all necessary dosage strengths, which forces the recipient of the drug to split their tablets. Tablet splitting is a commonly used method to obtain the proper dosage of drugs who don’t have the right dosage in the form of one tablet. The method is in theory simple, in that breaking the tablet in half should give half the dosage and so on, but it’s not always certain that splitting a tablet will give evenly divided parts, which in turn could lead to complications if the patient would receive too much or too little of the active substance. Purpose: The purpose of this report was to find out if patients had difficulties with splitting their tablets, if their tablets usually were evenly divided and if they ever experienced changes in the effect of their medication after splitting. To find out about all of this, patients from various pharmacies all over Sweden were interviewed and the answers of all patients were summarized in various tables for further examination and conclusion. Results: 171 patients were interviewed under a course of 2 weeks from 8 different pharmacies. Out of these, the majority of patients that required split tablets were between 66-75 years old and the majority of these were women. The drug that was split most often was Imovane® and in total, 71 % of the participants didn’t experience any problems with splitting the tablets while 20 % did experience problems. Conclusion: The results of this study show that while tablet splitting happens relatively often and several patients are prescribed drugs that require splitting even though the correct dosage is available in one tablet, there are relatively few patients that have problems with splitting, compared to the ones that did,. In addition, most patients  didn’t get any problems with their treatment after dividing. Granted, this is a small study compared to the whole Swedish population that split their pills and further studies are necessary in order to get a more concrete idea regarding how patients feel about splitting their pills.

Prescription of tablets is one of most common means for treatments of patients within the healthcare sector. Not seldom, drug manufacturers supply a limited number of tablet strengths, or physicians unnecessary prescribes a to high tablet strengths. This results in the situation where patients end up splitting tablets.  Another reason for splitting tablets is that they are voluminous, and thereby hard to swallow. Upon dividing tablets, fragments can become unequal in size, and parts of the tablets can crumble, leaving a tablet dose sometimes not compliant with government issued regulation, stated in different Pharmacopeias. Major parts of split tablets are prescribed to elderly people, who require lower dosages.  Some tablets are hard and small and elderly people have difficulties in dividing them, due to e.g. trembling and insufficient muscle strength in hands. The aim of this study was to investigate, pros and cons with splitting tablets, and how it´s practically done by the patient. What advice are given from staff in pharmacies to customers, in order to get it right. During two weeks, in March 2018, structured interviews were conducted on patients who had prescriptions on divided tablets. Among 7677 customers in eight pharmacies in Sweden 188 (2, 4 %) presented a prescription with split tablets. Of them, 171 accepted to participate in a survey to find an answer to the aim of this study. Out of the 171 customers 153 (89 %) divided their tablets. 74 (49 %) broke the tablets with their hands, 47 (31 %) with a knife and 22 (14 % ) use a device for dividing tablets.  The rest had recently received a prescription on a divided tablet.  Most common split tablets were within the ATC-codes C and N, cardiovascular and psychotropic drugs. They were split by 139 (81 %) of the customers. Within ATC-code N05 benzodiazepines 53 (31 %), C09 antidepressant 23 (13 %), N06 RAS 19 (11 %) and C07 betablocker 16 (9 %) divided tablets. Among the costumers who divided their tablets, 47 (28 %) said that the tablet size was not ideal to divide. About 36 (21 %) reported that they had difficulties dividing tablets; the number was highest among women. About 50 % of the customers had been given instructions by the pharmacist about how to split a tablet. The result of this study shows a need of lower strengths of some tablets, and that prescribers should be more aware and not unnecessary prescribe split tablets, since there are many especially elderly people that have difficulties in dividing them in equal parts.

Pharmaceuticals have been developed as long as humanity has suffered from diseases. It is something today’s people take for granted and is associated with strict rules as well as social initiatives. The purpose of pharmacies has developed from being an authoritarian part in healthcare to focusing on the customer and their needs. This particular role for pharmacies is one of the main focuses in this candidate thesis. A survey was performed at seven different pharmacies located at seven different sites in Sweden. The survey illuminates relevant questions around the dialogue between the customer and pharmacist. The communication between pharmacist and customer is an important aspect in the process of a purchase, because medicine has become more advanced and precise. The communication is a complicated procedure that requires to be mastered by pharmacists and also by customers at a specific point in time and place. This interplay creates customer satisfaction. The result showed that customers were generally reassured with the treatment of their medicine. The pharmacist gave relevant and enough information according to the answers on the survey. It showed that doctors still have the most trust amongst customers regarding the medicine information, thereafter the pharmacist. Possibly the reason for this depends on the relations between doctors and patients compared to pharmacists and customers. Even though pharmacists today have a major role when it comes to medical treatment and customers are satisfied, it is still common that they search for information in other ways. Digitalisation will probably affect this subject.

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Fetma är ett växande hälsoproblem, såväl i Sverige som i övriga världen. Idag räknar man med att cirka 10 % av männen och 12 % av kvinnorna i Sverige lider av fetma (BMI≥30). Komplikationerna till följd av fetma är många, och inkluderar många allvarliga sjukdomar och tillstånd. Typ 2-diabetes är en av dessa sjukdomar och risken att insjukna ökar kraftigt med ett stigande BMI. Man räknar med att cirka 90 % av alla som diagnosticerats med sjukdomen också uppvisar fetma. Grunden i all fetmabehandling utgörs av livsstilsförändringar, som kost och fysisk aktivitet. En viktnedgång på 5-10 % är ofta tillräckligt för att man ska se en förbättring av kardiovaskulära och metabola riskfaktorer. När en tillfredsställande viktnedgång inte uppnås genom livsstilsförändringar kan farmakologisk behandling bli aktuell. Ett av de läkemedel som idag är godkänt för behandling av fetma är orlistat (Xenical®). Läkemedlet verkar genom att hämma gastro- och pankreaslipaser, vilket resulterar i en minskad fettabsorption på cirka 30 %. Syftet med detta arbete var att undersöka orlistats additiva effekt på viktnedgång hos personer med en samtidigt mild minskning av kaloriintaget. Förutom viktnedgång har även dess effekt vid typ 2-diabetes, med avseende på HbA1C, fasteglukos samt förändringar i diabetesmedicinering undersökts i vissa studier. Metoden som har använts i detta arbete är en litteraturstudie. De artiklar som användes hämtades från databasen PubMed, och sammanlagt var det fem studier som granskades. Två studier som fokuserade på orlistats effekt på viktnedgång, och tre studier som fokuserade på både dess effekt på viktnedgång och typ 2-diabetes. Samtliga studier visade på en signifikant större viktnedgång hos orlistatbehandlade individer jämfört med placebogruppen. I tre av studierna låg viktnedgången mellan 3,9-6,5 kg, och i de övriga två studierna mellan 5,0-8,5 %. När det gäller HbA1C så minskades det med mellan 0,6-1,1 procentenheter och fasteglukos mellan 1,3-1,9 mmol/l. Det var även fler orlistatbehandlade som kunde minska, eller till och med upphöra med, medicineringen mot sin diabetes. Slutsats blir därför att orlistat kan vara ett användbart läkemedel i kampen mot fetma och dess riskfaktorer, som i det här fallet typ 2-diabetes.

Psoriasis är en kronisk inflammatorisk hudsjukdom som drabbar tre procent av Sveriges befolkning. Sjukdomen är en kombination av abnorm och snabb celldelning och en överreaktion i immunsystemet. Psoriasis kan variera i svårighetsgrad från lätt psoriasis till svår psoriasis men är ingen livshotande sjukdom. Sjukdomen kan dock påverka livskvaliteten kraftigt. Om man får psoriasis så har man fått psoriasis livet ut. Idag finns det ingen behandling som helt kan bota psoriasis, däremot finns det behandlingar som är symtomlindrande. Psoriasisbehandling blir därför alltid en långtidsbehandling. Eftersom huden är kroppens största organ kan det dagliga livet påverkas av tidskrävande och framförallt dyra behandlingar. Syftet med denna studie var att undersöka vilken av de olika tillgängliga biologiska behandlingarna mot psoriasis som har bäst effekt på kort respektive lång sikt. Metoden som användes var en litteraturstudie där inkluderade artiklar hämtades från PubMed. Sammanlagt baseras studien på fyra monoterapistudier och en meta-analys. Samtliga monoterapistudier av de biologiska preparaten adalimumab, efalizumab, etanercept och infliximab visade på en effektiv och säker långtidsbehandling hos patienter med måttlig till svår psoriasis. Den femte studien som var en meta-analys baserad på korttidsbehandlingar med biologiska läkemedel (alefacept, efalizumab, etanercept och infliximab) tyder på att infliximab har bäst effekt jämfört med de andra biologiska läkemedlen. Även om infliximab har bäst effekt vid korttidsbehandling är detta inte nödvändigtvis fallet vid långtidsbehandling. Alla de olika biologiska läkemedlen förefaller ge ungefär samma effekt vid långtidsbehandling. Jämförande studier som direkt undersöker vilket av de biologiska läkemedlen som är effektivast och som tolereras bäst av patienter med måttlig till svår plackpsoriasis är önskvärda i framtiden. / Psoriasis is a chronic inflammatory skin disease that affects three percent of Sweden's population. The disease is a combination of abnormal and fast cell division and over-reaction of the immune system. Psoriasis varies from moderate to severe and it is not a critical disease, but it can affect the quality of life considerably. If you have psoriasis you have it for life.Today, there is no treatment that can cure psoriasis completely but there are treatments that can relieve the symptoms. Therefore, psoriasis requires long-term therapy. Since the skin is the body's largest organ, the daily life is influenced by time-consuming and above all costly treatments. The aim of this study was to examine which of the available biological agents that has the best effect in the treatment of psoriasis, with a focus on long-term treatment. The method used was a literature study with articles acquired from PubMed. The study is based on four mono-therapy-studies and one meta-analysis. The mono-therapy-studies investigated the following biological agents, adalimumab, efalizumab, etanercept and infliximab which were all shown to be effective and safe for long-term treatment of patients with moderate to severe psoriasis. The fifth study, which was based on short-term treatments with biological agents (alefacept, efalizumab, etanercept and infliximab), indicated that infliximab has the best efficacy. Although infliximab may have the best effect in short-term treatments this may not be the case for long-term treatments. All biological agents had approximately the same effect in the long-term treatments.There is still a need for direct comparative studies examining which of the biological agents that is most effective and best tolerated for patients with moderate to severe plaque psoriasis.

The tumor microenvironment is important for tumor growth and progression, where the cancer associated fibroblast (CAF) is one central cell type. The CpG island methylator phenotype (CIMP) divides colorectal cancer (CRC) into three subgroups and in this study we investigate how the different CIMP-groups and adjacent fibroblasts affect each other. This was done with the aim of finding CIMP-specific markers and to see if different tumor-fibroblast interactions result in differently invasive tumors. Here we report that CIMP-negative tumors have increased expression of fibronectin, while CIMP-high tumors have reduced expression of E-cadherin, findings that were seen in both tumor tissue samples and tumor cell lines. We also show that CIMP-negative and CIMP-high cancer cells induce an alignment of the fibronectin fibers produced by the fibroblasts and that CIMP-high cancer cells migrate with directionality on these matrices. These findings indicate that the different tumor subgroups in fact induce different phenotypes in CAFs, resulting in CIMP-specific markers. They also indicate that CIMP-negative and CIMP-high tumors may induce an alignment of fibronectin in order to promote cancer cell migration and thereby also tumor invasion.

Colorectal cancer (CRC) has either an infiltrative or pushing growth pattern, and patients in the former group have a worse prognosis. Infiltrative tumours are linked to epithelial-mesenchymal transition, which in turn is associated with increased cellular migration. As there is no molecular model that entirely describes the difference between infiltrative and pushing configurations we investigated if differences found in cell junctions between tumour cells (in the core of the tumour) could explain the different growth patterns. A PCR array targeting cell junction genes was performed on one infiltrative and one pushing tumour. Thirteen genes were selected for verification by real-time qRT-PCR in additional tumours and normal tissue from the colorectum of patients. GJB3, Gap Junction Protein beta 3 (also known as Connexin 31) was the best candidate for separating tumours of different growth patterns. GJB3 was down-regulated in tumours compared to normal tissue, suggesting that it may act as a tumour suppressor, and it was further decreased in tumours with a pushing growth pattern. Silencing the expression of GJB3 in the colon carcinoma cell line SW480 did not affect the proliferation or the migration of the cells, suggesting that GJB3 by itself cannot regulate proliferation or metastatic spread.

Interleukin 33 (IL-33) is a dual function cytokine. It is a member of the IL-1 family and it acts as a pro-inflammatory factor (18 kilo Dalton, 18 kD) like other cytokines in IL-1 family. IL-33 is also a transcription factor (32 kD - form) which can suppress or activate gene transcription in diverse cases. A variety of cell types and tissues in the central nervous system (CNS) can release IL-33 after injury. The 18 kD IL-33 binds to the membrane receptor protein ST2 ligand, then regulates downstream gene expression, triggers cytokine synthesis, and modulates the immune system response. After traumatic brain injury (TBI) in the CNS, glial cells become key players in the nervous tissue response. Astrocytes undergo activation, proliferation, release pro-inflammatory factors and, as a consequence, a glial scar barrier around the injury is formed. Simultaneously, resting microglia are activated and able to remove debris. Lastly, oligodendrocytes together with microglia and astrocytes are activated and communicate with the immune system. In addition, as a severe kind of injury to the CNS, brain tumours share some similar characteristics of brain injury, such as hypoxia and inflammation. Therefore, IL-33 may play a role in neuroinflammation and also in brain tumours. In this project, our aim was to investigate the role of IL-33 and the IL-33/ST2 pathway in traumatic brain injury and brain tumours (e.g glioma). We found that IL-33 can influence the CNS immune resonse, and may be important in CNS pathology.

Background Osteoporosis is a disease with reduced bone mass and deterioration of bone structure, which leads to increased risk of fractures (1.9). Approximately one in four men and one in two women will at some time in life suffer a fracture due to osteoporosis. Supplemental calcium and vitamin D have long been a cornerstone of osteoporosis treatment. Drugs that are also used clinically for the treatment of osteoporosis include bisphosphonates, denosumab, selective estrogen receptor modulators (SERM), and strontium (3). Bisphosphonates are the most used osteoporosis drugs (4). The bisphosphonates alendronate, risedronate and zoledronic acid are interchangeable as first choice treatment of osteoporosis in postmenopausal women. Denosumab is another drug with antiresorptive effects that has been registered for the treatment of postmenopausal osteoporosis in recent years. Teriparatide (PTH) is an anabolic drug used for osteoporosis (3.6). Objective: The objective of this study was to examine the efficacy of alendronate, denosumab and teriparatide on fracture risk and bone mineral density in postmenopausal women with osteoporosis with the help of published meta-analyses and clinical trials. Result: Examined articles showed that alendronate treatment for at least one year reduces the risk of vertebral fractures with NNT = 17-50 and the risk of non-vertebral fractures with NNT = 50. PTH reduced the risk of vertebral fractures with NNT = 9.8 and non-vertebral fractures with NNT = 29. A statistically significant increase in BMD was also observed with an increase in BMD of 8.14% in the spine and 2.48% in the hip. PTH treatment compared with alendronate treatment was found to have a statistically significant difference (P=0.004) in the reduction of non-vertebral fracture risk with NNT = 10,4. Teriparatid treatment also showed more positive effects as compared to alendronate on BMD increases. Denosumab treatment for 36 months reduced the risk of fractures with a relative reduction of 68% for vertebral fractures and a relative reduction of 20% for non-vertebral fractures. Denosumab treatment for 12 months compared with alendronate therapy in postmeopausala women showed no statistically significant difference in fracture risk (p=0,19). The increase in BMD was, however, greater in the denosumab group than in the alendronate group, with 0.53% in the distal radius, 1.14% in the hip , 0.77% in the lumbar spine and 0.79% in the femoral neck.   Conclusion: These studies show that all three drugs, alendronate, PTH and denosumab, have good effects on reducing the risk of fractures in postmenopausal women. All drugs lead to increases in BMD in different parts of the skeleton. Reduction of fracture risk was greater for both denosumab treatment and PTH treatment compared to alendronate treatment, also BMD increased more with denosumab or PTH treatment compared with alendronate treatment. / Bakgrund Osteoporos är ett sjukdomstillstånd med reducerad benmassan och försämringar i benvävnadens struktur, som leder till att man lättare kan få benbrott. Ungefär var fjärde man och varannan kvinna drabbas någon gång i livet av en fraktur på grund av osteoporos. Tillägg av kalcium och vitamin D har länge varit en grundval inom osteoporosbehandlingen. Läkemedel som också används kliniskt för osteoporosbehandling inkluderar bisfosfonater, denosumab, selektiva östrogenreceptormodulatorer (SERM), samt strontiumsalt. Bisfosfonater är den mest använda gruppen av osteoporosläkemedel. Bisfosfonater som alendronate, risedronat och zoledronsyra vilka är utbytbara mot varandra räknas som förstahandsval i behandling av osteoporos hos postmenopausala kvinnor. Denosumab är ett annat osteoporosläkemedel med antiresorptiv effekt som registrerats för behandling av postmenopausal osteoporos de senaste åren. Teriparatid (PTH) är ett anabolt läkemedel som också används mot osteoporos. Syftet: Syftet med detta arbete var att med hjälp av publicerade meta-analyser och kliniska studier undersöka effekterna av alendronat, denosumab och teriparatid på frakturrisk och bentäthet hos postmenopausala kvinnor med osteoporos. Resultat: Granskade artiklar på postmenopausala kvinnor visar att alendronatbehandling under minst ett år minskar risken för vertebrala frakturer med NNT =17-50 och för icke-vertebrala frakturer med NNT=50. PTH minskade risken för vertebrala frakturer med NNT=9,8 och icke-vertebrala frakturer med NNT= 29. Statistiskt signifikant ökning i BMD förelåg också med 8.14% i ryggrad och 2,48% i höften. PTH behandling jämfört med alendronat visade en statistiskt signifikant skillnad (p=0.004) för minskning av icke-vertebrala frakturer med NNT=10,4. Teriparatidbehandling visade också mer positiva effekter jämfört med alendronat avseende ökningar i BMD. Denosumabbehandling i 36 månader minskade risken för frakturer med en relativ minskning på 68 % för vertebrala frakturer och en relativ minskning på 20% för icke-vertebrala frakturer. Denosumabbehandling under 12 månader jämfört med alendronatbehandling hos postmenopausala kvinnor gav ingen statistiskt signifikant skillnad (p =0.19) i frakturrisk. Ökning av BMD var dock större i denosumabgruppen än i alendronatgruppen, 0.53%  i distala radius, 1.14 % i höften, 0.77% i ländryggen  och 0.79% i lårbenhalsen. Slutsats: Studierna visade att alla tre undersökta läkemedel, alendronat, PTH och denosumab, har goda effekter på minskning av frakturrisk hos postmenopausala kvinnor. Samtliga läkemedel leder till ökning av BMD i olika delar av skelettet. Minskningen av frakturrisk var större för både denosumabbehandling och PTH-behandling jämfört med alendronat, även BMD ökade mer vid denosumab- eller PTH-behandling jämfört med alendronatbehandling.