Abstract [en] Title: Discrepancies in medication lists at hospital wards identified by medication reconciliation Authors: Anderberg M. Institute: Uppsala University, Uppsala, Sweden Background and objective: An accurate medication list is essential for a correct assessment of a patient´s condition at hospitals. Previous studies have shown that patients in emergency departments often are affected by discrepancies in medication lists at hospital admission. Less research has been done regarding discrepancies after transferring patients to medical wards. The aim of this study was to identify discrepancies in the electronic medical record in hospital wards for patients admitted via the emergency department. Design: Observational study. Medication reconciliation was performed by a pharmacist shortly after the arrival of patients from the emergency department. This included a patient interview and the investigation of the patient’s medical record. The discrepancies identified at the wards were classified as either omitted drug, wrong dose, additional drug, incorrect frequency or duplicate therapy. Descriptive statistics were used and the proportion of medication lists with at least one discrepancy was presented with 95 % confidence interval. Setting: Three medical wards at Capio S:t Görans Hospital in Stockholm.  Main outcome measures: The proportion of medication lists with at least one discrepancy. The mean value of discrepancies among all patients. Classification and categorization of discrepancies regarding type and ATC index.  Results: In total, 63 patients were included with a mean age of 63 years. At least one discrepancy was identified in 43 % (95 % CI 31-55) of the medication lists. 52 discrepancies were found in total generating a mean value of 0,83 ± 1,17 discrepancies per medication list. The two most common categories were Omitted drug(33%) and Wrong dose(33%). The most frequent drug class associated with medication discrepancies was Drugs for obstructive airway diseases.  Conclusion: 43 % of the patients had at least one discrepancy in the medication list. This indicates the importance of medication reconciliations at medical wards even though the medication list has been updated at the emergency department.

Background: Medications are used to treat, cure, or relieve symptoms of diseases, but there is a risk with the use of medications. Drug-related-problems are known to increase morbidity and mortality. Incorrect medical list and discrepancies in these lists can lead to drug-related problems as side effects, hospitalization, non-compliance, drug interactions and overtreated or undertreated patients. Discrepancies can be for example: more prescriptions than necessary, outdated prescriptions, i.e., medicines that will not be used, prescriptions with incorrect dosing and missing prescriptions i.e., medicines used by patients that cannot be seen in the medication list. Purpose:  The aim of this study was to investigate discrepancies in the Swedish prescription list "My saved prescriptions at the pharmacy". The secondary aim was to investigate how common it is to use this prescription list or the dosage label on the medicine packaging to know which medicines to use and which dosage. Methods: The data collection was performed by four pharmacy students at seven pharmacies in Sweden over a period of three weeks during Jan-Feb. 2021 where the prescription list was investigated together with patients to identify any discrepancies. The study included patients who was over 18 years old, spoke Swedish, had three or more prescribed drugs, and agreed to participate.  Results A total of 215 patients were interviewed, where 61% had one or more discrepancies in their medication list. A total of 1717 prescriptions were analyzed, of which 10% were double prescriptions (n = 167), 8% outdated prescriptions (n = 141) and 3% prescriptions with the wrong dosage (n = 42). When analyzing the primary sources of information used by patients to know which medicine to use, the printout of the list "my saved prescriptions at the pharmacy” dominated (n = 72).  Most used information source to know drug dosage was the dosage label on the medicine packaging (n = 112). Conclusions: It is important to have an updated and correct information in the medication list, to prevent drug-related-problems caused by discrepancies. It becomes even more important when we see that the medication list "My saved prescriptions at the pharmacy" and dosage label (containing the same information in the medication list), are the most used primary sources by patients to know which drug to use and in what dosage. Finally, results show a relationship between the number of prescribed drugs and the number of discrepancies that occur, and therefore we see more discrepancies in elderly patients who are usually ill and are being treated for several diseases.  There are opportunities for further research to study e.g., which drug-related-problems are caused by discrepancies in the medication list as well as the degree of danger in these problems. / Användning av läkemedel som avses behandla, lindra eller bota sjukdomar kan i vissa fall utgöra en risk för patientens hälsa. Läkemedelsrelaterade problem p.g.a. felmedicinering står för en stor andel av morbiditeten och mortaliteten bland patienter. En bidragande orsak är ofullständig information i patientens läkemedelslista.   Syftet med studien var att undersöka antalet avvikelser som förekommer i receptlistan ”Mina sparade recept på apoteket”. Studiens sekundära syfte var att undersöka vilka informationskällor som användes av patienter för att veta vilka läkemedel som ska adminstreras och i vilken dos dosering.  Studiens metod var att intervjua patienter som kom till apoteket för att hämta ut läkemedel till sig själva och uppfyllde inklusionskriterierna för att delta i studien. Studien utfördes av fyra farmaceutstudenter på sju olika apotek i fyra olika städer i Sverige som tillsammans med patienter gick igenom receptlistan för att identifiera avvikelser.  Resultatet blev totalt 1717 recept som studerades varav 21% hade avvikelser. Av recepten var 10% dubbla recept (n = 167), 8% inaktuella recept (n = 141) och 3% recept med fel dosering (n = 42). Vid analys av primära informationskällor som används dominerade utskrift av listan ”Mina sparade recept på apoteket” (n = 72) resp. doseringsetiketten på läkemedelsförpackningen (n = 112).  Resultaten visade även ett samband mellan ökade antal läkemedel och antalet avvikelser.  Avvikelser i läkemedelslistan Mina sparade recept är vanligt förekommande därmed är listan inte alltid aktuell. Det är vanligt att denna lista och doseringsetikett på läkemedels-förpackningar används som primära källor av patienter under deras behandlingstid vilket kan innebära en risk för läkemedelsrelaterade problem. En gemensam nationell läkemedelslista är en möjlig lösning till att förebygga läkemedelsrelaterade problem orskade av infromationsbrist i läkemedelslistor. Det är dock nödvändigt med läkemedelsgenomgångar för att bibehålla uppdateringen av listan.

Background: Type II diabetes is a common disease worldwide and several drug treatments are available. Some of the more recently approved drugs are DPP4-inhibitors, GLP analogues and SGLT2-inhibitors. Most of the Type II diabetes drugs (T2DMD) are prescribed by primary care physicians. To ensure rational drug use it is important to follow up prescribing patterns to design strategies and interventions that can improve drug treatment, since consequences of inappropriate drug use might be poor health outcomes and increased health costs. Aim: To study differences in the prescribing pattern of T2DMD among primary healthcare centres (PHC) at a macro level in Region Uppsala. Method: A cross-sectional study based on data collected from Region Uppsala’s data register. Data consisted of individuals over 25 years of age with at least one prescription of a diabetes drug from the Anatomic Therapeutic Chemical (ATC) group A10 prescribed within the period of January 2018 to June 2020. Results: There is a moderate difference in the prescribing patterns of T2DMD among different PHCs in Region Uppsala. Overall, a larger proportion of oral antidiabetic drugs (OAD) were prescribed compared to Insulins. Most PHC prescribed a larger proportion of long acting insulins than other Insulins. Among OAD, a larger proportion of Biguanide derivative where prescribed. DPP-4 inhibitors, Sulphonylureas and SGLT2-inhibitors were prescribed to almost the same extent. Conclusion: Overall, there is a minor difference in the prescribing patterns of T2DMD among different PHCs in Region Uppsala during the study period. Lately, prescribing of DPP4-inhibitors, SGLT2-inhibitors and long acting insulins have increased. / I detta fördjupningsprojekt studerades förskrivningsmönstren av typ II diabetesläkemedel i Region Uppsala. Studieresultaten vissa skillnader i hur olika vårdcentraler i Region Uppsala förskriver typ II diabetesläkemedel. Från början var hypotesen att icke-insuliner förskrivs i större utsträckning än insuliner. Vilket visade sig stämma överens med resultaten. I studien jämförs också skillnaden mellan förskrivning av icke-insuliner som funnits längre på marknaden och de nyligen godkända (DPP4-hämmare och SGLT2-inhibitorer). Resultaten visar en tydlig ökning i förskrivning av de nya läkemedlen under studieperioden. En anledning till detta kan vara läkemedels positiva farmakologiska effekter. I studien jämförs också skillnaden i förskrivningen av de olika insuliner i Region Uppsala. Resultaten visar att långverkande insuliner förskrivs i större utsträckning i jämförelse med andra insuliner, vilket är inte enligt rekommendationslistan för förskrivning av typ II diabetesläkemedel Studieresultaten kan användas för att fortsätta följa upp och förbättra kvalitén på diabetesvården i Region Uppsala. Ytterligare studier skulle till exempel kunna utgå ifrån hela populationen med en typ 2 diabetesdiagnos för att studera utfall även för andra interventioner än läkemedel. Dessutom behövs fortfarande kunskap om det är kostnadseffektiv att fler nya typ 2 diabetesläkemedel används. Studien ger kunskap om förskrivningen av typ II diabetesläkemedel i Region Uppsala. Studien kan användas som grund för dialog om förskrivningen av typ II diabetesläkemedel i regionen, så att denna optimeras och fler individer får adekvat behandling. Detta arbete är viktigt eftersom typ II diabetes är en mycket vanlig sjukdom där prevalensen ökar.  Denna studie är en tvärsnittsstudie baserat på sekundärdata från Region Uppsalas elektroniska medicinalt register och primärdata från två enkäter skickade till sjuksköterskor och läkare som jobbar på vårdcentraler med patienter med diabetes. Studien inkluderar data från de 26 offentliga vårdcentraler som hör till förvaltningen Nära, Vård och Hälsa i region Uppsala. Förskrivningsdata baseras på recept för ett diabetesläkemedel från Anatomic Therapeutic Chemical (ATC) gruppen A10, förskrivet mellan januari 2018-juni 2020.

Background and Objective: Comorbidity and especially cardiovascular diseases are common among patients with chronic obstructive pulmonary disease (COPD). The primary purpose of this study was to identify drugs for the treatment of cardiovascular diseases in COPD patients. The secondary purpose was to analyze whether the use of cardiovascular drugs differs between patients with mild and severe COPD symptoms.     Method: The study was a retrospective cross-sectional study of 421 COPD patients whose drug lists were analyzed and cardiovascular drugs were identified. These drugs were then divided into eight drug groups, based on the drug's ATC (Anatomic Therapeutic Chemical classification system) codes. Only patients with reported cardiovascular diseases were included in the analysis. Patients with mild and severe COPD symptoms were identified. Thereafter, the patients were divided into two groups based on the COPD symptoms. Chi-squared test was performed to see if the use of cardiovascular drugs differs between patients with mild and severe COPD symptoms.  Setting: Primary and secondary care patients with COPD in Gävle and Dalarna.  Main outcome measures: Identify and analyze the use of cardiovascular drugs in COPD patients with mild and severe symptoms.  Results: The results of the survey showed that cardiovascular drugs were used by 274 (65%) of the COPD patients. Among them, 66 % with severe COPD symptoms and 34 % with mild symptoms. The use of the eight cardiovascular drug groups were similar between patients with mild and severe COPD symptoms. There wasn’t any statistically significant difference in the use of cardiovascular drugs between patients with mild and severe COPD symptoms (p= 0,893).   Conclusions: There wasn’t any difference in the use of cardiovascular drugs among patients with mild and severe COPD symptoms. However, this result needs to be substantiated with a follow-up study with a larger study population and longer study time to be generalizable.

Background: Pressurized metered dose inhalers (pMDI) use propellants for pulmonary drug delivery. The propellants used in pMDI:s are strong greenhouse gases. The Powder dose inhaler (PDI) doesn’t use any propellants and contributes less to the carbon footprint. Aim: The purpose of this project is to present data on inhaler use in the Uppsala County Council in Sweden. This project aims to answer questions regarding pressurized metered dose inhalers (pMDI) carbon footprint, how prescriptions of inhaler types with lower carbon footprint compare with pMDI and how the Uppsala County Council compares with other county councils in Sweden. Methods: This cross-sectional study uses prescription data for collected inhalers in Uppsala County Council and similar county councils in Sweden. Calculations of carbon footprint of the propellants in pMDI:s and for the lifecycle of pMDI and PDI. Results: The study showed that the climate load from the greenhouse gases norflurane and apaflurane in pMDIs are 981 477kg CO2e in Uppsala County Council year 2020. Of all the county councils studied, the county council with the highest percentage of pMDIs use was Stockholm County Council, the Uppsala County Council was close second.  Conclusion: Uppsala County Council might need to review if there is a way to lower the amount of pMDI prescriptions to reduce its carbon footprint deviating from the rest of County Councils in Sweden. This project ties into Uppsala County Council goal of reducing the climate impact of medical anesthesia greenhouse gases with 10% by 2022 from 2018.

In order for a medication treatment to be considered successful, several roles and functions along the pharmacological treatment chain must function and cooperate effectively. The chain can most easily be described as five transitions; diagnosis, prescription treatment, dispensing, drug use and finally results and follow-up. Unfortunately, there are many problems and inefficiencies in the pharmacological drug chain. Unfortunately, those who study medication errors and their solutions have focused on individual parts of the pharmacological treatment system. However, for this reason, this study aims to develop a general framework for system analysis of inefficiencies along the pharmacological treatment chain. Due to the size of the problem, this project focused on medication adherence. Adherence can be defined as to what extent the patient follows the medication treatment plan. Adherence has many known problems and difficulties, among other things, it has major financial consequences. It can also be difficult to measure compliance, and there is no recognized perfect method. A system dynamic model is a theoretical image of a real system or object, which is a model used to understand the nonlinear behavior of complex systems. These models are useful when considering interventions and their effects when there are complex relationships. The project started with a literature study, and then went into data collection. Here, a search design and refinements were designed to find relevant articles. Once the articles were selected, the data was compiled from the articles and the analysis began. Here, factors and effects on adherence were identified as well as other interesting information from the articles. When the information was compiled and analyzed, the system dynamic model was created. The model was then sent via email to experts in the field to validation and revise the model. During the data collection, 23 relevant articles were found, compiled into 38 factors associated with compliance. In addition to these factors, 8 were excluded because they were too disease-specific or too ambiguous in their effect of adherence. The various articles studied many different chronic diseases, but hypertension was the most common. How adherence was measured in the articles also varied greatly, however, some form of self-report or questionnaire was most common method used. Three out of seven experts responded to the sent-out model and provided valuable comments. Although these are not sufficient to validate the model, their views showed that a validation can be designed in this way. The model would have to be sent to a larger set of experts and stakeholders, but because these experts are recognized in their fields, it gave weight to the results even though they were few reviewers. With the support of the literature and the experts’ statement, it was concluded that this model provides a good foundation and structure to continue to build upon. In addition, the model has proven to have many key relationships and cornerstones with important and relevant factors. It is also concluded that it is possible to translate the model into quantitative patterns, which is based on the fact that the factor itself can be translated quantitatively. Overall, it is also finally concluded that the model created in this project could be of great use in future projects when working towards a framework for system analysis of inefficiencies along the pharmacological treatment chain.

Bakgrund: Globalt drabbas 300 miljoner av depression och sjukdomen kan idag behandlas med både antidepressiva läkemedel och psykoterapi. Depression diagnosticeras utifrån klassificeringssystemen ICD-10 och DSM-5 och självskattats utifrån MADRS-skala. Sjukdomen kan delas in i följande svårighetsgrader: lätt/lindrig depression, medelsvår/måttlig depression och svår/djup depression. Vid val av antidepressiva läkemedel är det viktigt att ta hänsyn till svårighetsgrad, biverkningar och interaktioner.  Syfte: Syftet med denna studie är att kartlägga läkemedelslistor framtagna av Sveriges olika läkemedelskommittéer och beskriva val av läkemedelsbehandling vid depression för vuxna och äldre.  Metod: En dokumentanalys utfördes som lämpar sig till att kunna jämföra aktuell offentlig information. Datainsamlingen utfördes hösten 2022 med hjälp av Sveriges 21 olika regioners behandlingsrekommendationer för vuxna och äldre. En egen bedömningsskala med maximalt tre poäng utfördes för att lyckas bedöma regionernas läkemedelsrekommendationer.  Resultat: För vuxna rekommenderar 19 regioner vid lindrig-medelsvår depression sertralin, vid medelsvår-svår rekommenderar 13 regioner venlafaxin och vid svår rekommenderar sex regioner TCA där amitriptylin/klomipramin är mest förekomna. För äldre rekommenderar 13 regioner sertralin/mirtazapin/escitalopram vid lindrig-medelsvår depression, vid medelsvår-svår rekommenderar 13 regioner duloxetin/venlafaxin och vid svår rekommenderar två regioner duloxetin. Enligt den egna bedömningsskalan uppnås varierande antal poäng där totalt sju regioner uppnår maximal poäng.  Slutsats: SSRI var den vanligaste preparatgruppen som rekommenderades av regionerna vid medelsvår depression hos både vuxna- och äldre. Vid svår depression var den vanligaste preparatgruppen SNRI för äldre och TCA för vuxna. Enligt den egna bedömningsskalan var Läkemedelverkets och Socialstyrelsens rekommendationer mest vanligt förekomna källorna hos regionerna. / Background: Globally, 300 millions of people suffer from depression and the disease can today be treated with both antidepressants and psychotherapy. Depression is diagnosed from the classification system ICD-10 and DSM-5 and is self-assessed based on the MADRS-scale. The disease can be divided into the following difficulty level: light/mild depression, medium/moderate depression, and severe/deep depression. It is very important to consider difficulty level, side effects and interactions when choosing an antidepressant.  Aim: The aim of this study is to identify drug lists produced by Sweden’s different pharmaceutical committees and describe the choice of drug treatment for depression for adults and the elderly.  Materials and methods: A document analysis was performed which is suitable to be able to compare public information. The collection of data was performed autumn 2022 with the help of Sweden’s 21 different regions treatment recommendations for adults and the elderly. An own assessment scale was accomplished to judge the regions drug treatment recommendations. Results: For the adults, 19 regions primarily recommend sertraline for mild-moderate depression, for moderate-deep depression 13 regions recommend venlafaxine and for deep depression six regions recommend TCA where amitriptyline/clomipramine are most common. For the elderly, 13 regions primarily recommend sertraline/mirtazapine/escitalopram for mild-moderate depression, for moderate-deep depression 13 regions recommend duloxetine/venlafaxin and for deep depression two regions recommend duloxetine. According to the own assessment scale a varying number of points were achieved, were a total of seven regions achieved maximum points.  Conclusions: SSRIs were the most common drug group recommended by the regions for moderate depression for both adults and the elderly. In deep depression the most common drug group was SNRIs for the elderly and TCAs for adults. According to the own assessment scale the Swedish- Medicines Agency and Social Welfare Board are most common sources in the regions.

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.

Introduction: Alzheimer's disease is a neurodegenerative disease that initially manifests itself primarily as impaired short-term memory and impaired language ability. The course of the disease is mainly due to an atrophy in the brain that can be attributed to the protein amyloid B and tau. Monoclonal antibodies that target Alzheimer's disease often have a high rate of cerebral edema, where proteinaceous fluid leaks into the extracellular space of the brain and creates edema. Some of the most common symptoms for amyloid-related imaging abnormalities (ARIA-E) are headache, dizziness, and blurred vision. In a few cases, patients with ARIA-E need to be hospitalized for observation, but most show a decline in ARIA-E within one to two months. Objective: To investigate the frequency of ARIA-E in clinical studies of monoclonal antibodies to patients with Alzhiemer's disease and to investigate the role of the ApoE4 allele in the development of ARIA-E. Method: Literature review of five RCT studies based on four different monoclonal antibodies. PubMed was used to search for the RCT-studies. Results: ARIA-E varies between different types of antibodies. ARIA-E usually occurs early in treatment when the degree of amyloid b is highest in the brain. Most cases are asymptomatic and treatment resumes within 1-2 months. Conclusion: Aria-E frequency correlates strongly with dose strength as well as APOE4 -status and most of the incidences are asymptomatic. With the right titration and individually selected drugs as well as individual dosages a safe care can be established for patients with Alzheimer's disease. If treatment is initiated at an early stage, the risk of side effects is reduced and more neurons can be saved from atrophy. The combination of several different types of medicine will further reduce the risk of ARIA-E.

Background: There is a widespread and increasing use of psychoactive prescription drugs, such as opioid analgesics, anxiolytics, hypnotics and anti-epileptics, but their use is associated with a risk of drug use disorder, misuse and abuse. Today, these are globally recognized and emerging public health concerns. Aim: The aim of this thesis is to estimate the prevalence of psychoactive prescription drug (PPD) use disorders, misuse and abuse, and to investigate the association with some potential risk factors. Methods: A study using register data from forensic cause of death investigations investigated and described cases of fatal unintentional intoxication with tramadol (Study I). Based on register data on spontaneously reported adverse drug reactions (ADRs) reported cases of tramadol dependence were investigated and summarised (Study II). In a study in suspected drug-impaired drivers with a toxicology analysis confirming the intake of one out of five pre-specified PPDs, the prevalence of non-prescribed use was assessed and associated factors were investigated (Study III). From a cohort of patients initiating prescribed treatment with pregabalin, using data on prescription fills, a study investigated longitudinal utilisation patterns during five years with regards to use of the drug above the maximum approved daily dose (MAD), and factors associated with the utilisation patterns (Study IV). Results: In the first study, 17 cases of unintentional intoxications were identified, of which more concerned men, the median age was 44 years and the majority used multiple psychoactive substances (alcohol, illicit drugs and prescription drugs). The second study identified 104 spontaneously reported cases of tramadol dependence, in which more concerned women, the median age was 45 years, and a third reported a history of substance abuse and 40% of past psychoactive medication use. In the third study, more than half of the individuals suspected of drug-impaired driving used the drug without a recent prescription. Non prescribed use was most frequent in users of benzodiazepines and tramadol, and was more likely in younger individuals and in multiple-substance users. In the last paper five longitudinal utilisation patterns were found in pregabalin users, with two patterns associated with a particularly high risk of doses above the maximum approved dosing recommendation. This pattern of use was associated with male sex, younger age, non-urban residency and a recent prescribed treatment with an antiepileptic or opioid analgesic drug. Conclusions: This thesis shows that psychoactive prescription drug use disorders, misuse and abuse occur and may have serious and even fatal consequences. The prevalence varies between different drugs and populations. Abuse and misuse seem to be more common in young people. Fatal intoxications and misuse of prescribed drugs may be more common in men, while drug use disorders following prescribed treatment may be more common in women and non-prescribed use equally distributed between women and men. Individuals with a history of mental illness, substance use disorder or abuse, or of past use of psychoactive medications are likely important risk groups. In summary, the findings suggest a potential for improvements in the utilisation of psychoactive prescription drugs. The results may be useful in the planning of clinical and regulatory preventive interventions to promote the rational, individualised and safe use of such drugs.