<p>Adherence to medical ordination is low and for long-time medication it is estimated to be as low as 50 percent. Depending on the prescribed drug this could lead to adverse effects and/or loss of effect of the drug. Information about why a drug is prescribed is important patient information and is thought to help increase compliance with the physician’s prescription. According to results from a recent study of visits to the emergency room at Karolinska Universitetssjukhuset in Solna, Stockholm, medically related problems were the cause in about 30 percent of the cases. According to the same study 11 percent of these visits were due to problems with patient adherence. Specifying indications on prescriptions could be a way to enhance drug compliance. Furthermore clinical indications on prescriptions ensure that the correct drug is administered for the correct condition. The purpose of this study was to examine how often indications were found on prescription labels on anti-parkinson drugs, ATC-code N04.</p><p>Prescription data were collected from the Swedish Prescribed Drug Register. A total of 22 994 prescriptions of anti-parkinson drugs dispensed in October 2007 were transferred from the register in Excel-files. Information about the patient’s year of birth and gender was included as well as the name of the drug, ATC-code, amount of drug dispensed, strength and information about the prescribed drug. Prescriptions lacking information about the patient’s year of birth or gender was excluded as well as prescriptions for animals.</p><p>On prescriptions for anti-parkinson drugs, with a total of 22 939 prescriptions after exclusion, half of them were provided with indication labelling. Indication labelling was more common on prescriptions for women. As regards patients older than 85 years, 63 % of the prescriptions were labelled with indication.</p> / <p>Abstract</p><p>Patienters bristande följsamhet till förskriven ordination är ett av de stora läkemedelsproblemen av idag. Att förse varje recept med användningsområde i doseringstexten är ett sätt att försöka förbättra patientföljsamheten. Sådan information är även av vikt för expedierande farmaceut för att kunna göra en professionell bedömning om huruvida valt läkemedel, dos och styrka passar ihop med sjukdomsbilden. Tidigare studier har visat att det är långt ifrån på alla recept som användningsområde finns angivet. Syftet med arbetet har varit att undersöka på hur stor andel av recept inom ATC-grupp N04 (medel mot parkinsonism), det finns angivet användningsområde i doseringstexten. En jämförelse mellan dopaminerga och antikolinerga medel inom gruppen gjordes även. Data från Apotekets transaktionsdatabas tillhandahölls i form av excel-filer. Dessa innehöll information från recept utskrivna på ATC-grupp N04, som expedierats på apotek i Sverige oktober 2007. Information om patientens födelseår, kön, läkemedlets ATC-kod, benämning, förpackningsstorlek, styrka och doseringstext erhölls. De recept som saknade uppgift om kön eller födelseår exkluderades, likaså recept till djur. Exkluderade från undersökningen var även dosdispenserade läkemedel. Av de 22 939 expedierade recepten inom ATC-grupp N04 som uppfyllde inklusionskriterierna innehöll hälften av dessa användningsområde i doseringstexten. Användningsområde på recept var något vanligare hos kvinnor än hos män. Högst frekvens av informationen sågs på recept till personer 85 år och äldre. Resultatet för recept på dopaminerga medel var i stort jämförbart med huvudgruppens resultat, dvs. hälften av recepten innehöll användningsområde, det var vanligast på recept till personer över 85 år och informationen var mer frekvent förekommande på recept till kvinnor. De antikolinerga medlen hade användningsområde angivet på 38 % av recepten, det var ungefär lika vanligt förekommande på recept till kvinnor som män, och en minskning av förekomsten av användningsområde sågs på recept till personer över 74 år. Sammanfattningsvis kan konstateras att förskrivare alltför ofta underlåter att skriva ut användningsområde i doseringstexten trots nyttan det skulle innebära för både patient och farmaceut.</p><p>2008:F16</p>

<p>Abstract</p><p>Restless legs syndrome (RLS) är ett kroniskt neurologiskt tillstånd som karakteriseras av en intensiv oro och obehagliga krypningar djupt inne i benen som förekommer i vila. Besvären upplevs som svårast på kvällen och natten och lindras av att man rör på sig. Hos majoriteten av de som lider av RLS förekommer även ofrivilliga periodiska benrörelser i sömn (PLMS) vilket medför täta mikrouppvaknanden. Detta försvårar övergång i djupare sömn vilket kan i sin tur leda till allvarliga sömnstörningar. Man kan dela in RLS i en primär form och en sekundär form beroende på om syndromet kan klarläggas till någon bakomliggande orsak. Eftersom syndromets patofysiologi fortfarande är oklar finns inte någon botande behandling men det finns bra möjligheter att lindra symtomen.</p><p>Dopaminagonister har visat ha god effekt på både RLS-symtomen och PLMS vid behandling av primär RLS. Effekterna brukar man känna av redan vid låga doser. Vid behandling med dopaminagonister kan biverkningar förekomma så som illamående, huvudvärk, sömnighet etc. Dopaminagonister kan användas som monoterapi vid behandling av RLS-symtom eller i kombination med andra läkemedel.</p><p>Syftet med denna litteraturstudie var att undersöka vad de två ”icke-ergolina” dopaminagonisterna pramipexol och ropinirol har för olika effekter vid behandling av RLS. Metoden som använts i detta arbete har varit en litteraturstudie. Fem artiklar valdes ut från databasen PubMed samt att befintlig litteratur söktes på Kalmars Högskolebibliotek och Örebros sjukhusbibliotek. Samtliga studier visade signifikant förbättring på RLS-symtomen med pramipexol- och ropinirolbehandling jämfört med placebo. Däremot krävs fler randomiserade kontrollerade studier av hög kvalitet som bland annat undersöker den långsiktiga behandlingseffekten av dessa preparat och att man koncentrerar sig på de kvarstående problemen kring negativa effekter som kan uppstå vid behandling.</p><p>2008:F25</p>

<p>Irritable bowel syndrome (IBS) är en komplex sjukdom som yttrar sig på många sätt</p><p>och i olika svårighetsgrad. Nuvarande behandling riktar sig mot att behandla varje</p><p>symtom var för sig. Hos patienter med svåra symtom är detta inte alltid tillräckligt.</p><p>Efterupptäckten att tricykliska antidepressiva (TCA) kan lindra IBS hos</p><p>diarrédominanta patienter ökade intresset för andra antidepressiva läkemedel. Detta</p><p>ledde till att selektiva serotoninåterupptagshämmare (SSRI) blev intressanta. SSRI</p><p>preparat har visats ha en smärtlindrande effekt hos patienter med IBS och en parallell</p><p>har dragits till signalsubstansen serotonin som finns i både hjärnan och tarmen. Därför</p><p>har forskare nu funnit det intressant att undersöka SSRI-läkemedel.</p><p>Syftet med denna litteraturstudie var att undersöka om SSRI-läkemedlet citalopram</p><p>kan ha en lindrande effekt vid IBS olika symtom, såsom förstoppning, diarré,</p><p>uppsvälldhet, gaser och framförallt smärta i buken.</p><p>Artiklarna för studien var hämtade från databasen PubMed och Kalmar Högskolas</p><p>egen databas Elin. Fem artiklar ingick i arbetet och alla är undersökningar där</p><p>citalopram administrerats till människor och råttor.</p><p>Två av artiklarna visade på symtomlindring hos patienter med IBS medan de i tre av</p><p>artiklarna inte kunde visade någon signifikant (p>0.05) skillnad mellan citalopram och</p><p>placebo.</p><p>På grund av stora placeboeffekter vid IBS i de olika studierna är det svårt att avgöra</p><p>om citalopram har en symtomlindrande effekt hos patienter med IBS. De olika</p><p>studiedesignerna gjorde det också svårt att dra några egentliga slutsatser. Det finns</p><p>dock en viss indikation att citalopram skulle kunna fungera symtomlindrande hos</p><p>patienter med IBS. Dock behövs mer studier inom området med fler patienter för att</p><p>kunna befästa om citalopram har en symtomlindrande effekt vid IBS.</p><p>2008:F27</p>

Background Malaria remains a global health issue with the burden unevenly distributed to the disadvantage of the developing countries of the world. Nigeria, a middle-income country in sub-Saharan Africa, is one of the countries with high malaria burden in the world. As a socioeconomic issue, the high level of poverty in Nigeria is an important factor that reinforces the persistent malaria burden in the population. Poverty contributes to the malaria burden as it can affect integral aspects of malaria control like treatment seeking behaviours, access to preventive measures and treatment. Presently, there have been renewed efforts in the global malaria control resulting in reductions in the global malaria burden over the last decade. However, the development of resistance to artemisinin-based combination therapies threatens the sustainability of the present success in malaria control. The mechanism behind the development and spread of antimalarial drug resistance is a complex one with multiple factors in play. Nevertheless, antimalarial drug use behaviours remain critical drivers of drug resistance as they can affect some of the other factors. This study adopted a social epidemiological stance in exploring existing antimalarial drug use behaviours that have the potential to drive drug resistance development and spread. The study went further to investigate the role of socioeconomic factors in the adoption of the identified behaviours when treating malaria. Methods An exploratory mixed methods research design was adopted in this study. This design involved an initial systematic review of the literature to create a holistic picture of what is known about the issue under study. The systematic review informed the design of a qualitative study involving the use of interviews to explore the existing antimalarial drug use practices in the Nigerian population; and the different socioeconomic factors influencing the behaviours. The qualitative interviews informed the design of a measurement instrument and hypotheses that were tested in a survey with larger number of participants from Nigeria Findings The important malaria treatment seeking and drug use behaviours identified in this study were the practice of mixing drug for malaria treatment, presumptive treatment of malaria, sharing of malaria treatment course, and saving antimalarial drugs for future use. When symptoms are experienced, socio-economic factors, like the educational level, type of settlement, and 12 | P a g e household income level, tend to determine the treatment behaviours and therefore inform and determine the experience of malaria illness. There were statistically significant relationships between socioeconomic measures and drug use behaviours like the use of mixed drugs, stopping treatment to save drugs, sharing of antimalarial drugs, adherence to recommended dose and time of administration, presumptive treatment and use of recommended drugs for malaria treatment. These behaviours differ regarding the specific socioeconomic measures that are significantly associated with them. Discussion Physical and social environments can place constraints on an individual’s choices as well as that of a population. As shown in this study, education, income level and type of settlement, as structural factors, affect the decision on how to seek malaria treatment, what antimalarial drug to get, and how to use antimalarial drugs. Practices like mixing, stopping treatment to save drugs, and sharing of antimalarial drugs with others have the potential to encourage the development and spread of antimalarial drug resistance by exposing the parasite to sub-therapeutic doses of antimalarial drugs. Also, mixing of drugs paves the way for the sale of fake as well as expired antimalarial drugs thereby affecting malaria morbidity and illness experience. Conclusions and Recommendations In malaria campaigns, there is need to broaden the scope of antimalarial drug resistance control strategies to include strategies targeted at improving the socioeconomic status of people in malaria endemic areas. The informal health facilities were significantly associated with most of the reported resistance-promoting drug use behaviours like mixing; as such efforts to improve the way antimalarial drugs are used should target these facilities. Population-wide improvements in income level, educational level, environmental and structural conditions of the rural areas in malaria endemic settings like Nigeria, will encourage behavioural changes on how antimalarial drugs are used.

Renal transplantation is the definitive treatment for the end-stage renal failure. Despite concerted efforts to increase the number of available organs there remains a wide gap. Kidneys with small renal cell carcinoma have been used for transplantation after ex vivo resection of tumours with excellent results. Concerns regarding the behaviour of tumour under standard immunosuppression prevent this source from being popularised. We studied tumour behaviour with standard immunosuppression and immunosuppressives with anti-proliferative properties and the effect of MHC matching on tumour behaviour. Luciferase labelled Wistar rat kidney tumour cells were injected subcutaneously into Wistar or Lewis rats to mimic well and poorly matched groups. These were divided into groups receiving Cyclosporine, Sirolimus high and Sirolimus low dose and Leflunomide. Effects of matching on tumour rejection were studied by immunosuppression withdrawal in half of the animals within each group. Tumour progression was monitored with IVIS spectrum imaging system. When the immunosuppression was continued for the length of the study period with Cyclosporine immunosuppression, the tumour continued to grow in both strains. With high dose Sirolimus, the tumour was eradicated within 2 weeks in both Wistar and Lewis rats (p < 0.05). Both strains receiving low dose Sirolimus also eradicated the tumour within four weeks of treatment (p < 0.05). In Leflunomide group, 4/7 animals rejected the tumour within the 4 weeks of study period (p < 0.05). To study the effects of rejection and matching on the tumour behaviour, the immunosuppression was stopped after 2 weeks of treatment and the animals followed for another two weeks to study these effects. After treatment withdrawal, the tumour rejection was noted which was significantly stronger in poorly matched animals than in well-matched animals (p < 0.05) in cyclosporine treated animals. These results appeared to be in line with our hypothesis, that newer immunosuppressive medications with anti-neoplastic effects may be better options after transplanting kidneys after small tumour ex-vivo resection. Acute rejection showed significant ability to lead to tumour eradication, more effectively in less well-matched animals than well-matched combinations. Thus perhaps clinically, recipients of such restored kidneys should be less well matched and immunosuppressed with agents with anti-proliferative properties. These results will need to be replicated with further studies including closely monitored clinical studies before it can be popularised at a significant new source of precious organs.

Gastroretentive drug delivery systems might enhance bioavailability of some drugs formulated in sustained release dosage forms by providing a longer residence time in the stomach. The aim of this study was to develop and evaluate a swellable floatable gastroretentive drug delivery system utilizing an effervescent mechanism.

Three different techniques have been studied to evaluate the effect of topical formulations on human skin. Measurement of electrical skin impedence as a non-invasive technique for the in-vivo assessment of skin hydration is reassessed, with the aim of evaluating the moisturising effects of various therapeutic treatments. Monitoring of baseline untreated forearm skin suggests wide inter- and intra- subject variations. The equivalent circuit appropriate for modelling the skin has been elucidated. For the electrode configuration commonly used short-circuiting of the electrodes occurs during product assessment. The performance of laser Doppler flowmetry for monitoring cutaneous vasodilation has been evaluated using various nicotinic acid esters as model compounds. Results indicate that the time taken for the nicotinates to elicit a response by the flowmeter, is the most reproducible parameter. This response varies with the concentration of nicotinate applied. The importance of the physicochemical properties of the products is emphasized. The final technique examined here has been developed to assess the irritation potential of surfactants. The concentration of surfactant required to elicit human red blood cell lysis has been used as an index for measuring surfactant irritation and the results compared those obtained by human patch and rabbit eye tests. For a series of surfactants and surfactant mixtures containing different number of moles of ethylene oxide, the results suggest, the higher the concentration required to induce haemolysis, the lower will be the irritation.

Various neurotoxins were investigated to assess their suitability for developing an animal model to study partial brain BH4 deficiency, neurotransmitters and behavioural alterations. Acute dosing with lead, diethylstilboestrol (DES), amphetamine and scopolamine produced no significant changes in rat brain BH4 metabolism though total biopterins in the liver were significantly reduced by lead and DES. Acute starvation of adult rats decreased brain biopterins. This loss of biopterins may be due to enhanced oxidative catabolism of the active cofactor caused by glutathione depletion. Dietary administration of a BH4 biosynthesis inhibitor, DAHP, consistently decreased brain total biopterins in weaner rats but did not alter the levels of DA, NA, 5-HT or metabolites. However the DAHP diet also induced a marked reduction in food intake. Rats subjected to an equivalent degree of food restriction without inhibitor showed significant but less severe reductions in brain biopterins and again no effect on transmitter levels. DAHP produced a significant decrease in locomotor activity and rearing. This could not be ascribed to reduction in food intake as animals subjected to just dietary restriction showed an increase in these activities. As gross brain levels of DA, NA and 5-HT were unaltered by DAHP the behavioural changes associated with the induced deficiency in brain total biopterins might not have been mediated through the action of these compounds. Although localised changes in neurotransmitter levels may have been obscured by gross analysis it is also possible that the behaviour changes were mediated by a role of BH4 not yet elucidated. Long-term administration of a high aluminium low calcium diet to mice produced no effect on gross brain total biopterins, catecholamines, serotonin or choline acetyltransferase activity though significant behavioural changes were observed.

The current outlook for patients suffering malignant glioma is poor, with suboptimal delivery of agents across the blood-brain barrier, migration of tumour cells to areas that are not exposed to chemotherapeutic assault and the ability of tumour cells to repair DNA damage caused by anti-proliferative agents. The objectives were to demonstrate the potential of targeting the mitochondria of glioma cells through the use of tricyclic antidepressants and to show that the success of this approach is largely dependent on the metabolic capacity of the patient and the expression of the norepinephrine transporter on glioma cells. A range of tricyclic agents were screened against a panel of tumours using MTT, ATP-TCA and Annexin-V assays; the metabolic capacity of seventeen glioma patients was assessed through HPLC-MS/MS sampling of plasma Clomipramine concentrations and cytochrome P450 drug metabolism enzyme genotyping via real-time PCR; the presence of the norepinephrine transporter was elucidated through immunohistochemical, immunocytochemical, Western blotting and realtime PCR techniques and finally apoptotic potential was determined by screening tumours (retrospectively and prospectively) via real-time PCR. Chemosensitivity results show that Clomipramine (the range for five tumours tested was 42.57 ± 16.58 μM) and Nortriptyline (the range for four tumours tested was 30.22 ± 14.81 μM) were the most effective agents when tested in the MTT assay and Norclomipramine (the range for five tumours tested was 7.65 ±3.53 μM) and Nortriptyline (the range for five tumours tested was 33.15 ± 13.72 μM) were the most effective agents when tested using the ATP-TCA assay. Annexin-V flow cytometry supported these results and further evidenced that Clomipramine induces apoptosis in malignant glioma. The genotypic status of CYP2D6 and CYP2C19, combined with plasma levels of Clomipramine/Norclomipramine achieved in vivo, showed that mutations in the CYP2D6*2X3 allele significantly affect the metabolism of Norclomipramine (p<0.05). Immunohistochemical, immunocytochemical and Western blotting techniques demonstrated the presence of the norepinephrine transporter (encoded by the SLC6A2 gene) on glioma cells, however real-time PCR results suggest that the exons within the SLC6A2 gene contain splice variants. Taqman low density array of retrospective tumour samples revealed variation in the expression of apoptotic genes, with no discernable pattern, and that it is possible to modulate the expression of these genes by exposing SNB-19, DK-MG and UPAB glioma cells to tricyclic antidepressants, Procarbazine, Dexamethasone and Valproic acid. Evidence from this study demonstrates that tricyclic antidepressants provide a new approach to mitochondrially-mediated therapy for malignant glioma that express the Norepinephrine transporter, which overcomes the resistance to targeting proliferation and growth facto

Introduction This thesis looks at the pharmacist’s contribution to the capture of medication errors and preventing harm reaching patients. It has several components: an analysis of annual surveys of interventions made by pharmacists at a large teaching hospital, a re-coding of these surveys to see how many interventions were the result of prescribing errors, and an experiment in A&E where the pharmacist drafted the first prescription chart. Methods One-week surveys of pharmacist interventions were regularly made at Southampton General Hospital between 1999 and 2009. These were analysed for trends, then recoded to identify the proportion that were caused by prescribing errors. In addition, a controlled trial was conducted to investigate the effects on prescribing error rate, of a pharmacist obtaining an accurate medication history in A&E, then transcribing the data onto the first inpatient prescription. Key findings In the period 1999-2001, the average number of interventions in each week long survey was 575 and during 2005-9 it was 973. This was a statistically significant increase. More interventions were recorded as serious in the latter period. The rate of interventions also increased from between one per every five and seven patients (31 to 45 prescribed items) to one per every one to two patients (8 to 20 items). The severity of interventions also increased, with between one and five deaths avoided each week. Almost three quarters of pharmacists’ interventions (73.9%) were triggered by prescribing errors, giving an error rate of 644 prescribing errors per week, or 6.2 per 100 prescribed items. These data are in contrast to the Trust submitting 918 error reports per year to the NPSA, the majority of which were administration errors reported by nurses. Nearly a half (45.3%) of all prescribing errors occurred during the admission phase of the hospital episode. Two thirds (67.1%) of prescribing errors detected were errors of omission - things that had not been done. Prescribing errors of commission occurred mainly during the inpatient phase and errors of omission during the admission phase. A quarter of prescribing errors were planning errors. These were failures to follow guidelines, failures to review patients’ prescriptions, manage interactions, and adjust dosage in liver or renal failure or in response to TDM results. One fifth (21.7%) of the patients had events or symptoms that contributed to the admission that could be explained by the medicines they were consuming. Over half of these were potentially avoidable by better monitoring or product selection. A pharmacist working in A&E to obtain complete and accurate drug histories, then transcribing the data onto the first prescription, produced a trend to reduction in the generation of errors throughout the whole hospital episode. Conclusions Analysing pharmacist’s interventions is a useful method of investigation prescribing errors and ways to stop them happening. First prescriptions written by pharmacists should provide an effective means of reducing errors which may be promulgated throughout the hospital stay.