Impact on accuracy in elderly patients’ medication list, introducing pharmacy-led medical reconciliation at the Emergency department in a Swedish hospital. Background and objective: Discrepancies in patients‘ medication list is a well-known problem and contribute to preventable medication errors. Medication errors could increase morbidity and mortality and are cost-driving to the Health Care System. The primary objective was to investigate if a pharmacist-led medical reconciliation at the Emergency department could increase the accuracy in medication lists for patients at the age of 75 years and older, with five or more drugs in their initial medication list. The second objective was to categorize the discrepancies and the drugs causing them. Study design: Intervention study with retrospective control group. In the intervention group, patients received a medical reconciliation at the Emergency department. In conformity with the retrospective control group, the intervention group also received a medical reconciliation at the hospital ward. All medical reconciliations where pharmacy-led. Discrepancies identified at the medical reconciliation at the ward, were quantified and categorized. Drugs causing discrepancies were categorized by the ATC-index. Descriptive statistics, Chi2-tests and T-tests were performed.  Setting: The Emergency department at the hospital of Kristianstad, four wards at the larger emergency hospital in Kristianstad and two wards at the smaller local hospital in Hässleholm in Sweden Main outcome measures: Numbers of discrepancies in patients ‘medication list identified at medical reconciliation at hospital ward after having an initial medical reconciliation at the Emergency department (intervention) or not (control). Category of discrepancy and ATC-index of the substance causing the discrepancy. Results: In control group (n=65), 170 discrepancies were identified, on average 2,6 discrepancies/medication list. In intervention group (n=65), corresponding figures were 44 and 0,7 respectively. The difference between the groups was significant (p <0,0001).  The main category of discrepancy was “commission of a medication” in the control group and “route of administration” in the intervention group. Paracetamol was the most common drug to cause discrepancies in the control group, zopiklon and furosemid in intervention group. Conclusion: Pharmacy-led medical reconciliation at the Emergency department significantly reduced the number of discrepancies in patients´medication list.

<p>There are today strong incentives for an increased understanding of material properties and manufacturing processes to facilitate the development of new technologies in the pharmaceutical industry. The purpose of this thesis was to suggest methods requiring a low sample amount for characterization of technical properties of powders.</p><p>Compression analysis was used to evaluate the formulation relevance of some compression equations. Using the mechanics of single granules to estimate powder functionality was part of this work. It was concluded that the formability of granular solids and the plasticity of single granules could be determined with compression analysis by using the Kawakita model for single components and binary mixtures of ductile granules.</p><p>Further on, the fragmentation propensity of solid particles could be estimated from compression analysis by using the Shapiro equation, enabling indicators of both the fragmentation and the deformation propensity of particles to be derived in one single compression test.</p><p>The interpretations of the compression parameters were only valid if the influence of particle rearrangement was negligible for the overall compression profile. An index indicating the extent of particle rearrangement was developed and a classification system of powders into groups dependent on the incidence of particle rearrangement was suggested as tools to enable rational interpretations of compression parameters.</p><p>The application of compression analysis was demonstrated by investigating the relevance of the mechanics of granular solids for their tableting abilities. The plasticity of single gran-ules was suggested to influence both the rate of compactibility and the mode of deformation, and consequently the maximal tablet strength. The degree of granule bed deformation was shown to be a potential in line process indicator to describe the tableting forming ability.</p><p>This thesis contributes to a scheme, suitable in formulation work and process control, to describe manufacturability of powders for an enhanced tablet formulation technology.</p>

<p>Trombin är ett trypsinliknande serinproteas som har stor del i kroppens reglering av blodets fluiditet och koagulation genom att det klyver faktorer som slutligen leder till att blodet kan koagulera och fibrin bildas. Syftet med det här projektet har varit att syntetisera fragment som designats med datorgrafiska metoder på Astra Zeneca och sedan analysera fragmenten med affinitetskromatografi med trypsin immobiliserad på kiselgelspartiklar. I projektet har även ett nytt koncept prövats, nämligen att analysera reaktionsblandningarna direkt med hjälp av trypsinkolonnen utan att först isolera och rena föreningarna. De designade fragmenten har syntetiserats med standardmetoder, bl.a. har N,N’dicyklohexylkarbodiimid (DCC) använts. DCC är ett kopplingsreagens som kopplar ihop aminer med karboxylsyror genom skapande av en amidbindning, peptidbindning. Ibland då lite mer komplicerade peptider skall göras, kan aminoänden eller karboxyländen skyddas med en skyddsgrupp, för att dessa inte ska reagera under reaktionssteget och för att man ska få den peptiden man är ute efter. Vätskekromatografi-masspektrometri, LC-MS har använts för identifiering av reaktionblandningarna (substanserna). Resultaten visade att två av de framställda föreningarna retarderades på trypsinkolonnen, vilket innebär att de växelverkar med trypsin och att s.k. hits, träffar erhållits. Synteserna verkar ha gått bra, då LC-MS har visat att det är rätt produkt som finns i kolven. Projektet har visat att det går att designa fragment som man syntetiserar och sen analyserar med AFC-MS. AFC-MS har dessutom visat vara en lämplig metod för screening av svagt bindande fragment.</p> / <p>Through different, intricate mechanisms, the body regulates the coagulation and the fluidity of the blood. This is an important part of the hemostasis if for example bleeding occurs, or to provide the body with oxygen and nutrition.</p><p>Thrombin is a trypsin like serine protease that plays an important role in this process since it is cleaving factors that eventually lead to coagulation of the blood and production of fibrin.</p><p>The aim of this project has been to synthesize fragments that have been designed with computer graphical methods by Astra Zeneca and then to analyze the fragments with affinity chromatography that has trypsin immobilized on silica particles. The project also introduces a new concept i.e. to analyze reaction mixtures on the trypsin column without first isolating and purifying the compounds.</p><p>The design fragments are synthesized by earlier reported standard methods. N, N'-dicyclohexylcarbodiimide (DCC) was used as coupling reagents to form amide or peptide bonds between carboxylic acids and amines.</p><p>In some of the reactions the amino group or the carboxylic groups of the amino acid were protected, to prevent these from interfering in the reaction and avoid to formation of unwanted substances. After the reactions the protecting groups were removed in different ways. If it is attached to the amine as a Boc-group (the most common protecting group to protect amino groups) it would be removed with trifluoracetic acid, and if the carboxyl group was protected, the protecting group would be removed with catalytical hydrogenolysis, for example by adding sodium hydroxide. To analyze if the right product has been acquired, analyzes with liquid chromatography-masspectrometry has been performed.</p><p>The results showed that two of the prepared fragments were retarded on the trypsin column meaning that they interact with trypsin i.e. hits were obtained.</p><p>The results showed that the two fragments that were analyzed with the trypsin column did retard a bit, which implies that they interact with trypsin. The synthesis seems to have been successful since the liquid-chromatography has shown that the right product has been made. This project has proven that it is possible to design fragments with computer graphical methods before synthesizing and analyzing with AFC-MS. AFC-MS has also been shown to be a suitable method for screening of weak binding fragments.</p>

Introduktion: Bensodiazepiner har ända sedan de introducerats till marknaden varit mycket populära och är bland de mest förskrivna läkemedlen. Trots populariteten samt den höga användningen är bensodiazepiner en problematisk läkemedelsgrupp med anledning till deras höga beroendepotential. Bensodiazepiner ska enligt behandlingsrekommendationer endast förskrivas som sista alternativ och användas under en begränsad period för att undvika beroendeutveckling, vilket oftast inte blir fallet i primärvården. Syfte: Syftet var att undersöka hur användningen av bensodiazepiner har sett ut mellan 2006 och 2014 och om beroendepotentialen var en möjlig faktor till hypotesen att användningen minskat– för att uppmärksamma problem med användningen av dessa läkemedel. Material och metoder: Artiklar hämtades från databaser som PubMed samt Google Scholar. Statistiken över användningen hämtades från Socialstyrelsens statistikdatabaser och presenterades i form av tabeller och grafer. Resultat: Denna studie undersökte om just beroendepotentialen var en möjlig faktor till hypotesen att användningen minskat – och hypotesen stämmer. Statistiken visade att användningen av många bensodiazepiner har minskat markant under den perioden som undersöktes; som mest troligt beror på de nya riktlinjerna och behandlingsrekommendationerna som tagits fram mellan 2009-2010. Trots att användningen av bensodiazepiner minskat stadigt har istället en ny trend upptäckts; att bensodiazepinbesläktade substanser, som zopiklon, ökar markant. Detta innebär att behoven av farmakologisk behandling fortfarande är densamma då användningen av bensodiazepiner och bensodiazepinbesläktade läkemedel inte har varierat signifikant under den undersökta perioden. Konklusion: Nya selektiva bensodiazepiner med obefintlig risk för beroendeutveckling och smalare biverkningsprofil är under utveckling; dessa kommer med störst sannolikhet lösa många av beroendeutvecklings-problemen som för närvarande uppstår vid användning av bensodiazepiner och besläktade substanser i primärvården. / Introduction: Ever since benzodiazepines were introduced to the market they have been very popular and are among the most prescribed drugs. Despite the popularity and the high usage of benzodiazepines, this group of drugs is problematic due to their high dependence potential. Benzodiazepines should according to treatment guidelines only be prescribed as a last option and be used for a limited period of time to avoid the development of dependency - which is often not the case in primary care. Aim: The aim was to examine the usage of benzodiazepines between 2006 and 2014 and if the dependency potential was a possible factor to the hypothesis that the use has decreased – in order to draw attention to the problems associated with benzodiazepines. Methods: The articles were retrieved from the databases PubMed and Google Scholar. Statistics on the usage were taken from the Board's statistical databases. Results: This study investigated if the dependency potential was a possible factor to the hypothesis that the usage of benzodiazepines have decreased – and the hypothesis is correct. Statistics showed that the usage of many benzodiazepines have declined significantly during the period examined; most likely due to the new guidelines and treatment recommendations developed between 2009-2010. Although the usage of benzodiazepines declined steadily; a new trend was discovered, namely the prominent increased usage of benzodiazepine-like drugs such as zopiclone. This means that the needs of pharmacological treatment is unchanged since the usage of benzodiazepines and benzodiazepine-like drugs have not varied significantly during the examined period. Conclusion: New selective benzodiazepines with non-existent risks of development of dependency as well as a narrower side effect profile is under development. These will most likely resolve many of the dependency issues currently arising from the usage of benzodiazepines and related substances in primary care.

Bakgrund: I Sverige förekommer epilepsi hos 1-2 % av alla hundar. De första anfallen visar sig oftast när hunden är mellan ett och sex år gammal. Det nuvarande förstahands­preparatet är fenobarbital, en substans som ökar tröskeln för elektrisk stimulering av motorcortex samt minskar monosynaptisk transmission som leder till minskad neuronal retbarhet. I februari 2013 registrerades ett nytt antiepileptikum med det verksamma äm­net imepitoin. Imepitoin är en partiell agonist som binder till bensodiazepinsätet på GABAA-receptorn. Det förstärker de GABAA-receptormedierade effekterna på neuro­nen samt har en svag kalciumblockerande verkan. Syfte: Arbetets syfte var att undersöka om imepitoin har förutsättningar att bli det nya förstahandspreparatet vid behandling av idiopatisk epilepsi. Vidare var syftet att under­söka i vilken utsträckning imepitoin fungerar som antiepileptikum samt vilken biverk­ningsprofil det har. Resultat: Behandling med imepitoin gav en sänkning av antalet epileptiska anfall per månad (MSF), liknande den som erhölls vid fenobarbitalbehandling. Imepitoin sänkte MSF både som monoterapi och i kombination med fenobarbital eller kaliumbromid. Biverkningsprofilen var överlag skonsammare för imepitoin jämfört med fenobarbital. Fenobarbital visade en leverpåverkan medan imepitoin påverkade kolesterolvärdet. Slutsats: Imepitoin har en antiepileptisk effekt, liknande den som fås vid behandling med fenobarbital. Behandling med imepitoin kan ske både som mono- samt kombina­tionsterapi. Den mildare biverkningsprofilen talar för användning av imepitoin. Samti­digt har fenobarbital använts under en längre tid så biverkningar vid långtids­användning är mer välkända än de vid imepitoinanvändning. / Background: In Sweden, approximately 1-2 % of all dogs suffer from epilepsy. The first seizures often occur when the dog is between one and six years old. In Sweden the first-line drug is phenobarbital, a substance which increases the threshold of electrical stimulation in the motor cortex. It also decreases synaptic transmission which leads to decreased neuronal excitability. In February 2013 a new antiepileptic drug was regis­tered with imepitoin as active substance. Imepitoin is a partial agonist which binds to the benzodiazepine binding site at the GABAA receptor and amplifies the effects medi­ated by GABAA receptors at the neurons. Additionally, imepitoin has a weak calcium channel blocking effect. Objective: The main aim of the study was to examine if imepitoin should be the first-line drug instead of phenobarbital when treating dogs diagnosed with idiopathic epi­lepsy. A further aim was to look into which effect imepitoin had in controlling the epilepsy and which adverse effects were experienced when dogs are treated with imepitoin. Results: Treatment with imepitoin resulted in a decrease in monthly seizure frequency (MSF), similar to the decrease seen upon treatment with phenobarbital. Imepitoin was decreasing MSF both when used as monotherapy and in combination with phenobarbital or potassium bromide. The adverse effects were in general less severe with imepitoin than with phenobarbital. Treatment with phenobarbital affected the liver while treatment with imepitoin affected the cholesterol levels. Conclusion: Imepitoin has a good antiepileptic effect, similar to that of phenobarbital. Treatment with imepitoin can be used both as monotherapy and in combination with other antiepileptic drugs. Less severe adverse effects makes imepitoin a possible choice for treating idiopathic epilepsy in dogs. On the other hand, phenobarbital has been used during a long period of time and adverse effects of long term use are therefore better known than for imepitoin.

<p><strong>Bakgrund: </strong>I dagens vårdarbete är behandling av venösa bensår en vanlig omvårdnadsåtgärd. Smärta, immobilitet samt social isolering relaterat till venösa bensår, är några av de faktorer som påverkar patientens livskvalitet. <strong>Syfte: </strong>Syftet med litteraturstudien var att beskriva hur sjuksköterskan på bästa sätt kan främja läkningen av venösa bensår. <strong>Metod: </strong>Beskrivande litteraturstudie sammanställd utifrån 14 kvantitativa samt sju kvalitativa studier publicerade mellan åren 2001 till 2009. Databaserna Cinahl och PubMed användes i sökningen av vetenskapliga artiklar. Sökorden som användes var Leg Ulcer, Nursing, Activity, Pain, Venous leg ulcer, Treatment, Management, Exercise, Bandages samt Psychological. <strong>Resultat: </strong>De omvårdnadsåtgärder som visade sig ha stor betydelse för sårläkning var kompression/sårvård, fysisk aktivitet, psykologiskt stöd samt eftervård. Sjuksköterskans kunskap och förmåga att kunna se patienten som en helhet var av stor vikt för god omvårdnad och förbättrad sårläkning. <strong>Slutsats: S</strong>juksköterskor behöver förbättra sina kunskaper angående sårvårdsbehandling. Sjuksköterskan bör ha en holistisk syn på patienten.</p><p> </p>

<p> </p><p>Studiens syfte var att med en huvudsakligen kvantitativ ansats 1) undersöka hur receptarier i Kalmar län upplever sin arbetssituation vid expedition av läkemedel till djur, genom att undersöka hur den personliga kompetensen, ansvarskänslan och de befintliga informationskällorna upplevs, samt 2) undersöka synen på ett eventuellt införande av tillsyn av farmaceuter och möjligheten till utdömande av disciplinära påföljder då farmaceutens yrkesutövning vid expedition av läkemedel till djur inte skett på ett föreskrivet sätt. Idag bär ingen myndighet ansvaret för dessa två företeelser.</p><p>En skriftlig enkät postades till 94 receptarier i Kalmar län. Av de tillfrågade receptarierna valde 55 % att delta. Enkätformuläret bestod totalt av 24 frågor av övervägande kvantitativ karaktär vars svarsalternativ utgjordes av kvalitativa variabler. Av enkätformulärets 24 frågor hade två stycken öppen karaktär.</p><p>Majoriteten av deltagarna tycktes uppleva sin arbetssituation vid expedition av läkemedel till djur som förhållandevis god och endast ett fåtal deltagare förmedlade en negativ ton i svaren. Receptariernas ansvarskänsla i sin yrkesroll framstod som hög och en receptexpedition till djur anses som likvärdig med en receptexpedition till människa. Flertalet av receptarierna var obekanta med avsaknaden av tillsyn och disciplinära påföljder, men ansåg att det finns ett behov av kontroll och var överlag positiva till ett eventuellt införande av sådan. Majoriteten av receptarierna trodde dock inte att arbetssituationen skulle påverkas nämnvärt av utökad kontroll. Studiens deltagare gav dock uttryck för att det finns behov av mer utveckling inom området, såsom utbildning och bättre informationskällor om läkemedel för djur.</p><p>Då studiens bortfall var 45 % samt då studiens validitet och precision troligtvis är låg, bör försiktighet iakttas vid extrapolering av studiens resultat till Sverige i övrigt.</p><p> </p>

<p>Cetirizine, an H₁-antihistamine, is prescribed for allergic disorders. It exists as a racemic mixture, with levocetirizine being the active enantiomer. The central nervous system side-effects of H₁-antihistamines are caused by their penetration into the brain. In this thesis the plasma pharmacokinetics, transport across the blood-brain barrier (BBB) and H₁ receptor occupancy of cetirizine enantiomers was investigated <i>in vivo</i> in guinea pigs. The transport across the BBB was quantified using the microdialysis technique. Stereoselective brain distribution was investigated by measuring both unbound and total concentrations in plasma and brain. The time aspects of the H₁ receptor occupancy of levocetirizine was studied in the brain and the periphery.</p><p>The plasma pharmacokinetics of cetirizine was stereoselective with clearance and volume of distribution of levocetirizine being approximately half that of dextrocetirizine. This was mainly due to the differences in plasma protein binding of the enantiomers. The stereoselectivity in brain distribution indicated by the partition coefficient K_p (total AUC ratio brain to plasma) was caused by stereoselective plasma protein binding. The transport across the BBB measured in this thesis by the unbound partition coefficient K_p,uu (unbound AUC ratio brain to plasma) was the same for the two enantiomers. Binding within the brain was also not significantly different. The H₁ receptor occupancy of levocetirizine in brain lagged behind the plasma concentrations whereas it was not delayed with respect to the brain concentrations. This indicates that the delayed brain H₁ receptor occupancy of levocetirizine is caused by a slow transport across the BBB.</p><p>In summary, the results of this thesis emphasize the importance of measuring both the unbound and total concentrations in blood and brain to characterize stereoselective brain distribution. The thesis also emphasize the importance of taking local brain pharmacokinetics into consideration in understanding pharmacokinetic-pharmacodynamic relationships of drugs with central activity.</p>

<p>Cefuroxime is a renally eliminated antibiotic used against a variety of different bacterial infections. The pharmacokinetics (PK) for cefuroxime was studied in 97 hospitalized patients using population analysis. To be able to measure cefuroxime in human serum a new sensitive analytical method was developed using mass spectrometry detection. The method was validated and shown to be sensitive and selective. Cystatin C was found to be a better covariate for cefuroxime clearance compared to the traditionally used creatinine clearance (CLcr). This relation might be useful when designing dosing strategies for cefuroxime and other renally eliminated drugs. </p><p>The time-courses of the biomarkers C-reactive protein (CRP), serum amyloid A (SAA), interleukin-6 (IL-6) and body temperature were studied for the first 72 hours of cefuroxime treatment and was related to the duration of illness previous treatment with cefuroxime and to time to step-down of treatment. When duration of illness was short, CRP and SAA were showed increasing levels. None of the biomarkers could be used to differentiate between early or late step-down of therapy.</p><p>By use of known PK and pharmacodynamic (PD) principles, dosing strategies based on CLcr for cefuroxime were estimated using minimization of a risk function. The risk function was constructed with the aim to expose patients to cefuroxime concentration above minimum inhibitory concentration (MIC) for 50 % of the dosing interval and to minimize the amount of drug administered in excess to reach the aim. Based on evaluation using wild type MIC distributions for <i>Escherichia coli</i> and <i>Streptococcus pneumoniae</i> improved dosing strategies were selected.</p><p>In vitro experiments were performed exposing <i>Streptococcus pyogenes</i> to constant concentration of benzylpenicillin, cefuroxime, erythromycin, moxifloxacin or vancomycin. A semi-mechanistic PK/PD model characterizing the time-course of the antibacterial effect was developed using all data simultaneously. Internal validation showed the model being predictive and robust. </p>

<p>The use of catanionic drug-surfactant mixtures was proven to be an efficient novel method of obtaining prolonged drug release from gels. It was shown that various commonly used drug compounds are able to form catanionic mixtures together with oppositely charged surfactants. These mixtures exhibited interesting phase behaviour, where, among other structures, vesicles and large worm-like or branched micelles were found. The size of these aggregates makes them a potential means of prolonging the drug release from gels, as only monomer drugs in equilibrium with larger aggregates were readily able to diffuse through the gel. When the diffusion coefficient for drug release from the formulation based upon a catanionic mixture was compared to that obtained for the drug substance and gel alone, the coefficient was some 10 to 100 times smaller.</p><p>The effects of changes in the pH and ionic strength on the catanionic aggregates was also investigated, and this method of prolonging the release was found to be quite resilient to variations in both. Although the phase behaviour was somewhat affected, large micelles and vesicles were still readily found. The drug release was significantly prolonged even under physiological conditions, that is, at a pH of 7.4 and an osmolality corresponding to 0.9% NaCl.</p><p>Surfactants of low irritancy, capric and lauric acid, may successfully be used instead of the more traditional surfactants, such as sodium lauryl sulfate (SDS), and prolonged release can still be obtained with ease.</p><p>Some attempts to deduce the release mechanism from the proposed systems have also been made using transient current measurements, dielectric spectroscopy, and modelling of the release using the regular solution theory. In these studies, the previous assumptions made concerning the mechanism responsible for the release were confirmed to a large extent. Only small amounts of the drug existed in monomer form, and most seemed to form large catanionic aggregates with the oppositely charged surfactant.</p>