Malignt melanom är den tredje vanligaste cancersjukdomen i Sverige och drabbar både kvinnor och män. Det kännetecknas av en växande mörk fläck större än 5 mm som oftast uppstår i befintliga nevi, dock kan det även börja som ny förändring i huden. Malignt melanom bör misstänkas om gamla nevi ändrar storlek, form, växer snabbt, kliar och blöder. Den vanligaste formen är ytligt spridande malignt melanom som botas med kirurgi. Om tumören inte opereras bort, kan den med tiden sträcka sig ner i huden och ge metastaser. Behandlingen av melanom som spridit sig beror på i vilket stadie (I-IV) tumören befinner sig, där stadie IV är det allvarligaste. Prognosen vid malignt melanom har länge varit dålig men nu finns det immunterapi som ger bättre totalöverlevnad (OS) och en längre progressionsfri överlevnad (PFS). CTLA-4-hämmare, ipilimumab och PD-1-hämmare, nivolumab alternativt pembrolizumab är T-cellsaktivernade antikroppar som används vid melanombehandling. Syftet med detta arbete var att undersöka vilken behandling som ger bättre klinisk nytta med avseende på bättre OS och längre PFS hos patienter med malignt melanom, om behandling med ipilimumab som monoterapi eller i kombination med nivolumab eller pembrolizumab är att föredra? Detta är en litteraturstudie där fem artiklar om effekten av ipilimumab som monoterapi samt i kombination med nivolumab eller pembrolizumab ensamt analyseras. Alla fem studier hämtades från Pubmed. Patienter som fick kombinationsbehandlig av ipilimumab + novilimumab fick en bättre OS och en längre PFS jämfört med patienter som fick ipilimumab som monoterapi. Efter en medianuppföljningstid på 3 år var median PFS 2,9 månader (95% konfidensintervall (CI), 2,8 – 3,2) för ipilimumabgruppen jämfört med 11,5 månader (95% CI, 8,7 – 19,3, p <0,001) i ipilimumab+nivolumabgruppen. Det var 34% patienter som överlevde efter tre år med ipilimumab ensamt jämfört med 58% med kombinationsbehandling. Kombinationsbehandling gav bättre effekt på OS och PFS men på bekostnad av flera toxiska, behandlingsrelaterade biverkningar. Det behövs mer forskning kring dessa läkemedel för att hitta biomarkörer och för att minska biverkningarna.

Androgenetic alopecia, also known as male pattern baldness, affects the majority of menat some point during their life. This can significantly damage the mental health of theindividuals suffering, especially at a young age. The pathophysiology is not fullyunderstood, but according to the scientific literature, it is mediated by androgensignaling in the scalp. A lack of androgen signaling completely eliminates thepossibility of developing the condition. This is the primary reason behind theeffectiveness of 5ɑ-reductase inhibitors, which effectively reduce androgen signaling bylowering dihydrotestosterone (DHT) concentrations by 98%. These medications areassociated with adverse effects such as sexual dysfunction and anxiety. Use of topicalforms of 5ɑ-reductase inhibitors and minoxidil is therefore on the rise. The purpose ofthis work was to examine the effectiveness of the combinations of the availabletreatments and the most effective monotherapy option. The results indicate thatdutasteride is the most effective option as monotherapy and that a combination of a5ɑ-reductase inhibitor and minoxidil is more effective than either on their own. It wasalso shown that microneedling is a valid adjuvant therapy to minoxidil.

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Background: Sepsis is a life-threatening organ dysfunction occurring during infections. Meropenem is a hydrophilic β-lactam carbapenem antibiotic. Its pharmacokinetic parameters are expected to change due to sepsis-induced physiological alterations and will thus require altered dosing strategies for optimal treatment of sepsis patients. Aim: This is a review with the purpose to compare the pharmacokinetics of meropenem between healthy adults and adult septic patients and explore the potential covariates that affect the pharmacokinetic parameters. Methods: Articles that were explored were collected from PubMed and were screened through inclusion and exclusion criteria. Results: Total of 19 articles were identified and selected. Participants in the studies were in the age range of 18–91 years, with the weight range of 37–120 kg. Volume of distribution at steady-state in the healthy participants had a median of 22.2 L, while the volume of distribution in septic patients had median 27.6 L. Clearance had median 13.89 L/h in healthy, compared to the median 10.43 L/h in septic. The median half-life was 1 h in healthy, whereas in septic, the median half-life was 2.5 h. Patients with fluid overload from fluid therapy had larger Vd & lower Cl, while patients with creatinine clearance < 50 mL/min had lower Cl. Conclusions: The physiological alterations developing in sepsis lead to an increase of the meropenem’s distribution and a decrease of its elimination, which is exacerbated by fluid overload. These findings could be a good starting point for building a physiologically based pharmacokinetic model of meropenem in sepsis.

Background: Pharmaceutical development has taken new ground in recent decades and placed new demands on the regulations. Since 2005, a risk management plan (RMP) has been required when applying for a first marketing authorization for a drug. The RMP forms the basis for how identified risks with the drug are to be managed. In the RMP for all drugs, regular measures (rRMM) such as summary of product characteristics (SPC) are applied. As only rRMM is not considered sufficient, additional measures (aRMM) are also applied, which can be, for example, extra training material for prescribers or patients. aRMM material is today distributed to prescribers via physical letters. Are aRMM materials communicated today in a way that fulfills the purpose of the regulations? Aim: The aim of this study is to gain knowledge through qualitative interviews with the pharmaceutical industry and regulatory authority in Sweden about how risks with drugs are communicated. Methods: Semi-structured individual interviews were conducted with 7 persons from the pharmaceutical industry and 1 person from the regulatory authority in Sweden, during March and April 2022. The interviews were transcribed and the data were analyzed with systematic text condensation. Results: The five main identified desired improvements in the communication of aRMMs are  these; 1. National common database for aRMM materials, 2. Flagging and availability in prescribing systems, 3. Swedish Medical Products Agency labeled materials, 4. Dialogue between healthcare, pharmaceutical companies and the pharmaceutical authority, 5. Diversity and availability of aRMM materials to patients.  Conclusion: aRMM is considered in itself to be an effective tool for managing and minimizing risks with medicines, but the measures lose effect and purpose due to lack of communication and understanding.

Introduction: Type 2 diabetes (T2D) increases in prevalence and generates significant diseaseburden, where impairment in hormonal systems, such as glucagon, is suspected to contribute to T2Ddevelopment. Covariates such as obesity is a known risk factor for T2D development. Additionally,higher fasting insulin and glucagon concentrations, stronger adrenocorticotrophic hormone- (ACTH)and cortisol-response during hypoglycemia have been demonstrated in obese individuals. In contrast,bariatric surgery has shown to result in diabetes remission, independent of weight loss. The effect ofglucose and insulin on glucagon, ACTH and cortisol have been well studied, but not modelledduring hypoglycemia. Aim: To develop a population model of glucagon, ACTH and cortisol response during hypo- andhyperglycemia by characterizing the relationship between glucagon and glucose/insulin as well asACTH and glucose, connected with cortisol and explore impact of covariates. Followed byinvestigating changes in the concentration-response relationships after Roux-en-Y gastric bypass(RYGB). Methods: Data from a cross-over study with one arm being hyperinsulinemic-eu/hypoglycemicclamp, and the second arm being a hyperglycemic clamp was combined with data from two crossoverdesign studies with arms being hyperinsulineamic-eu/hypoglycemic clamps, conducted beforeand after RYGB. The pre-surgical combined data was used to create a population model throughnon-linear mixed effect modelling where additional delay mediating through an effect compartmentwas investigated on all response variables. Various structural models were explored in order todescribe glucose and/or insulins effect on glucagon response. Glucose inhibition on ACTH production was described through a sigmoidal Imax-model, which was combined with a surge modelto describe ACTH production caused by circadian rhythm. Cortisol production was modelled asbeing driven solely by ACTH concentrations and covariate relationships were investigated through astepwise covariate model. The models were validated with statistical and graphical analysis. Results and discussion: Glucagon production was dependent on an individuals’ insulin sensitivityand fasting glucose and insulin concentration. Glucose inhibition on glucagon productioncontributed with 77 % of the total inhibition in comparison to insulin, which contributed with 23 %.Glucose concentration had a steeper exposure-response relationship in comparison to insulinconcentration on glucagon production. Despite insulin concentrations having smaller effect incomparison to glucose on glucagon production, insulin had significant impact on the models fit tothe data. ACTH and cortisol responses were accurately described, despite some misspecificationswhich were independent of glucose concentrations. Production of ACTH was dependent on insulinsensitivity and fasting glucose. Alteration in glucagon and ACTH production, together with insulinsensitivity was sufficient to describe changes after RYGB. This model can be used in optimal designgenerations where clamping technique is used as guidance of appropriate hypoglycemic clamplevels. Conclusion: A population model of glucagon, ACTH and cortisol response was developed using datafrom hypo- and hyperglycemic studies. Glucagon production was described as dependent onglucose and insulin and ACTH production was described as dependent on glucose, with the ACTHconcentration driving the cortisol production. Insulin sensitivity was found to affect baselineglucose and the sensitivity of ACTH to glucose. The model could describe post-bariatric surgerydata when adjusting the estimating of baseline glucagon and ACTH.

Background: Diclofenac is an analgesic, antipyretic and anti-inflammatory drug that may have harmful effects on the environment, It has contributed to the death of fish exposed to the substance through discharges into lakes and seas. Even birds, especially vultures, have died after exposure to diclofenac by consuming carcasses that were treated before they died. Aim: The purpose of this study was to assess the sales of diclofenac around Lake Mälaren. Method: Data were obtained from the Swedish eHealth Agencys statistics database Concise, for the time period 2018–2021. The counties studied were Uppsala, Västmanland, Södermanland and Örebro, which have waste water treatment plants with Lake Mälaren as the recipient. The amount sold in kg was calculated using DDD, number of packages and package size and analyzed by season, time, sales method and region. Results: Uppsala accounted for the highest sales of diclofenac of the counties studied and over-the-counter sales at pharmacies sold most of the various sales methods. During the winter there was an increase of sold diclofenac while no other seasonal variations were observed. Following the prescription in June 2020, sales of tablets and capsules decreased, while other forms of preparation were not affected. For each year studied, the number of kg of diclofenac sold has decreased. Conclusion: Sales of diclofenac have declined during the period of 2018-2021, which is positive from an environmental point of view as reduced use means reduced emissions to nature.  This data can be used to investigate farmacies and citys on a lower level.