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Läkemedel är en grupp kemikalier med effekt på olika fysiologiska processer hos människa och djur. Den största källa för läkemedelsrester är avloppsvatten från reningsverk. Eliminering av läkemedelssubtanser i reningsverk är ofta inte fullständig och läkemedelsrester i naturen har påvisats. Läkemedelsrester i vattenmiljö kan bioakumuleras och utgör toxisk risk för vattenlevande organismer. Med den globala utvecklingen av samhället förväntas exponeringen för läkemedelsrester öka. Ciprofloxacin, diklofenak och etinylestradiol tillhör läkemedelsgrupper för vilka effekter på miljö har observerats. En ökad kunskap om substansernas miljöskadliga egenskaper kan ge ett bättre underlag vid miljöriskbedömningar. Syftet med arbetet är att utifrån aktuell litteratur sammanfatta den kunskap och fakta som idag finns om ciprofloxacin, diklofenak och etinylestradiol med avseende på dessa ämnens miljöfarliga egenskaper och miljöpåverkan. Efter sökning och genomgång av vetenskapliga artiklar och rapporter inom området läkemedel och miljö sammanställdes en litteratur översikt över kända miljöeffekter av substanserna ciprofloxacin, diklofenak och etinylestradiol. Apotekens Service AB databas över uthämtade läkemedl på apotek (Concise) användes för kartläggning av användning av ciprofloxacin, diklofenak och etinylestradiol i Kalmar län och Sverige totalt. Ciprofloxacin, diklofenak och etinylestradiol har påvisats i vattenmiljöer i Sverige och andra länder. Kinolon-resistenta bakterier har påvisats i miljö. Toxisk effekt av diklofenak på t ex gamar i Asien har observerats. Etinylestradiol i miljö orsakar störningar av reproduktionsförmåga hos fisk. Det finns idag ingen dokumentation om läkemedel i miljö som pekar på en risk för humanhälsa. Enskilda hushåll står för den största delen av läkemedelsflöde till miljö. Uppmätt koncentration av läkemedelsrester i miljö ligger ofta mellan 1 ng/L upp till några µg/L. I miljön återfinns substanser huvudsakligen i en mix av olika ämnen. Det är viktigt med fortsatt forskning kring läkemedel i miljö för att kunna bidra till bättre framtida kunskap.

Title Prehospital pain management of traumatically injured adult patients Authors Benström S Institute Uppsala University, Uppsala, Sweden Background and objective Traumatic injuries are a major cause behind moderate and severe pain in a prehospital setting. Therefore, the aim of this study is to evaluate prehospital use of analgesics among adult traumatically injured patients treated within Tartu Ambulance Foundation by analysing how ambulance personnel evaluates and treats pain. Secondary aim is to map prehospital factors influencing the process. Setting and Method A retrospective, single-centre service evaluation study with the primary selection of 7526 electronic patient records (EPR) with the main diagnosis of S00-T98 (ICD-10) was conducted and a polyvariant logistic regression model was created to map factors that influence pain management. Main outcome measures Primary outcome measures were prevalence of pain evaluation and the use of analgesics. Secondary outcome measures were significant changes in odds ratios for prehospital-related factors that affected primary outcome measures. Results Mean age of the study population was 54 years (SD 22) and 775 (58.9%) were male. Out of all the patients in this study 529 (40.3%) received analgesics. Pain assessment before administrating analgesics was documented on 15.9% of EPRs. Nurses assessed pain 3.3 times (95% CI 2.0-5.3; p<0.001) more likely than physicians. The odds for receiving analgesics were 2.3 (95% CI 1.68-3.08; p < 0,001) times smaller when patients had consumed alcohol. Brief assignment (0-10 min) and hospitalisation reduced the odds of using analgesics by 3.6 times (95% CI 1.9-6.8; p<0,001) and 1.59 times (95% CI 1.13-2.24; p<0.007) respectively while lengthy assignments (>50 min) increased the odds by 3.4 times (95% CI 1.9-6.5; p<0,001). Monotherapy was chosen for 73.2% of patients while 24.6% received a combination of 2 and 2.2% a combination of 3 analgesics.   Conclusions   Current study showed that although nurses as brigade leaders are more likely to assess pain the overall prevalence remains low. Alcohol consumption among patients, short assignment times, and hospitalization decreased the odds for pharmacological pain management. Longer assignment times on the contrary were associated with increased odds. Improvements in pain management can be made in choosing between specific therapeutic options.

Background: The world prevalence of diabetes mellitus in 2019 was 8.3%, out of which 85-90% have type 2 diabetes mellitus (T2DM). Numerous drugs for treating T2DM are approved, and one of the newer classes of drugs are GLP-1 receptor agonists (GLP-1 RAs). In Sweden during 2015 to 2019, the number of patients using GLP-1 RAs has increased by 280%. Despite this, few studies have explored the experiences of patients using these drugs.  Aim: The aim of this study was to gain knowledge about how patients diagnosed with T2DM experience and understand their treatment with GLP-1 RAs in Sweden.  Methods: Individual semi-structural interviews were conducted with seven patients and three persons from the healthcare staff during October and November 2020 in Region Uppsala, Sweden. The data was analyzed qualitatively with systematic text condensation. Results: The four main findings were: 1) Both patients with great effect and less effect were satisfied with treatment and preferred GLP-1 RAs compared to their other treatments, 2) GLP-1 RAs may have an impact on lifestyle by effect on appetite and hunger and through the stability in glucose level, more freedom, 3) The preferred administration frequency depended on how easy it was to remember taking the drug, 4) Patients mostly understood their treatment as well as they wanted to, but regular initiation follow-ups and more explanations of decisions could increase treatment motivation and reduce anxiety.The healthcare staff confirmed these experiences by patients but assumed patients preferred weekly administrations compared to daily administrations.  Conclusions: Patients’ experiences of using GLP-1 RAs were positive and they described GLP-1 RAs as the best T2DM treatment they had.

Background and objectives: Medication is a source for improved health and increased life quality when used right but also a risk for unnecessary suffering when used wrong. Health personnel have a responsibility obligated by law to give patients individual information in order to enable safe usage and encourage concordance. This project aimed to investigate patients’ satisfaction with the information given about their cardiovascular medication by health personnel and to identify patients’ main sources of information. Design: This was a cross-sectional study with a duration of 2,5 weeks. The objectives were investigated using a survey. Participants were asked to rate the information they had received about their cardiovascular medications by health personnel on a response scale. Data was analyzed using descriptive statistics. Settings: Patients were recruited from four internal medicine wards in Trelleborg’s hospital. Main outcome measures: Satisfaction with information was categorized using the response scale. A score was calculated based on the survey in order to estimate the overall satisfaction and to compare subpopulations. Different options for information sources were listed in the survey. Results: Of 83 eligible patients 60 were included (32 women, age range 50-91). Populations satisfaction score median was 7,5 (5-10) out of 13. No significant difference could be found between subgroups based on gender (p=0,28), age (p=0,42) or educational level (p=0,85). Lowest satisfaction was seen with information about side effects, interactions and required life style changes while highest satisfaction was seen with information about the expected effect of the medicine and how to use it. Patients’ main sources for information were primary care physician, community pharmacist followed by the medicine leaflet which seemed to be the main source for information about side effects and handling of a missed dose. Conclusion: This study indicates that patients wish for more information linked to potential problems of their medicine usage. No difference was found between subgroups; however, this study is likely underpowered to confirm such a correlation. Although patients’ main sources were primary care physician and community pharmacist the medicine leaflet seemed to be an important complement and in some aspects a substitute for health personnel.

Abstrakt   Inledning Övervätskning har under senare tid väckt ett stort intresse då de kan leda till ödem och organdysfunktion. Patienter som vårdas på intensivvårdsavdelningar (IVA) administreras ofta intravenöst med vätskor i form av läkemedel och näring. Genom att ge mer koncentrerad administrering av läkemedel kan problem med övervätskning hanteras. På begäran av IVA i Västmanlands sjukhus begränsades fem läkemedelssubstanser där syftet för arbetet skulle studeras och besvaras. Syftet med denna studie var att undersöka om man på ett säkert sätt kan administrera de intravenösa läkemedelssubstanserna trimetoprim/sulfametoxazol, remifentanil, dexmedetomidin, erytromycin samt aciclovir i högre koncentrationän gängse praxis på en intensivvårdsavdelning. Metod Studien utfördes under perioden januari – maj 2020 på enheten för sjukvårdsfarmaci på Västmanlands sjukhus i Västerås. Metoden som användes för detta arbete var en litteratursökning i databaserna Pubmed och Cinahl. För att komplettera sökningen användes databaserna Eped, Micromedex samt UKCPAs handbok Minimum infusion volumes for fluid restricted critically ill patients. Resultat Totalt erhölls elva artiklar som inkluderades i studien. Trimetoprim/sulfametoxazol, remifentanil, erytromycin samt aciclovir kunde administreras i högre koncentration på ett säkert sätt än gängse praxis på IVA i Västmanlands sjukhus. Ingen artikel visade att dexmedetomidin kan administreras intravenöst i högre koncentration medan en studie visade att den kan administreras subkutant i högre koncentration. Slutsats Det fanns sparsamt med information inom detta område i dagsläget. Stabilitetsstudier var av hög kvalité, men kliniska studier saknas. Fyra av fem läkemedel kan antas  administreras i högre koncentration än vad IVA i Västmanlands sjukhus använder sig av idag. Som vidare forskning kan man göra studier på dexmedetomidin intravenöst eftersom den går att administreras subkutant i en högre koncentration. I framtiden krävs mer forskning inom detta område för att komma fram till fler resultat samt styrka resultaten av de studier som finns idag.

INTRODUCTION: Gastrointestinal cancers are one of the most fatal malignancies worldwide in both genders and all ages while breast cancer is the leading cause of cancer deaths in women internationally. Angiogenesis inhibitors and epidermal growth factor inhibitors are mainly used in colorectal and gastric cancer, while cyclin-dependent kinase inhibitors are mainly used in the treatment of breast cancer. However, studies of cost-effectiveness are needed to assess whether the high prices for these drugs can be justified with better outcomes and to what extent the total expenditure is acceptable for the health care system. Regional comparisons are important for future advancement within the field.   PURPOSE: The aim with this study was to describe whether there were any differences regarding the use of selected cancer drugs in Sweden’s six healthcare regions from 2005 to 2020.   METHOD: This research was a descriptive-comparative study. The aggregate-level data used in this paper was provided by the Swedish eHealth Agency and included the measurement total sales cost per 100,000 inhabitants of cyclin-dependent kinase inhibitors for both outpatient care as well as inpatient care. The angiogenesis inhibitors and epidermal growth factor receptor inhibitors were solely used in inpatient care. All data included both genders and all ages.   RESULTS: The majority of the cancer drugs studied in this paper had an uneven use and major differences were noted between the regions as regards the consumption of specifically bevacizumab and palbociclib in all the healthcare regions. Notable was the uptake of bevacizumab with approximately a four-fold difference between the southeast healthcare region and the west healthcare region in the year 2020. Palbociclib demonstrated circa seven-fold difference in uptake in the year 2020 between the west healthcare region and the north healthcare region.    CONCLUSION: Broadly, we can conclude that there are regional differences in the use of angiogenesis inhibitors and epidermal growth factor inhibitors in the treatment of colorectal cancer and gastric cancer. Cyclin-dependent kinase inhibitors also demonstrate regional differences in the treatment of breast cancer in Sweden’s six healthcare regions. It is of interest to further study why the regional differences exist in Sweden.

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<p>Studies of intestinal drug permeability have traditionally been performed in the colon-derived Caco-2 cell model. However, the permeability of these cell monolayers resembles that of the colon rather than that of the small intestine, which is the major site of drug absorption following oral administration. One aim of this thesis was therefore to develop a new cell culture model that mimics the permeability of the small intestine. 2/4/A1 cells are conditionally immortalized with a temperature sensitive mutant of SV40T. These cells proliferate and form multilayers at 33°C. At cultivation temperatures of 37 – 39°C, they stop proliferating and form monolayers. 2/4/A1 cells cultivated on permeable supports expressed functional tight junctions. The barrier properties of the tight junctions such as transepithelial electrical resistance and permeability to hydrophilic markers resembled those of the human small intestine <i>in vivo</i>. These cells lacked functional expression of drug transport proteins and can therefore be used as a model to study passive drug permeability unbiased by active transport. The permeability to diverse sets of drugs in 2/4/A1 was comparable to that of the human <i>jejunum</i> for both incompletely and completely absorbed drugs, and the prediction of human intestinal permeability was better in 2/4/A1 than in Caco-2 for incompletely absorbed drugs. The small intestinal-like paracellular permeability of 2/4/A1 thus enables better predictions of drug permeability in the small intestine than does Caco-2. </p><p>The studies of the paracellular route and its importance for intestinal drug permeability was also in focus in the second part of this thesis, in which a new principle for tight junction modulation was developed, based on the primary structure of the extracellular tight junction protein occludin. Peptides corresponding to the N-terminus of the first extracellular loop increased the permeability of the tight junctions, but lacked apical effect. This problem was solved by conjugation of one peptide to a lipoamino acid, resulting in two diastereomers with different effects. The L-isomer had a sustained apical effect, while that of the D-isomer was transient. In conclusion, conjugated occludin peptides constitute a new class of tight junction modulators that can enhance the tight junction permeability.</p>