Long-Term Follow-Up of Transsexual Persons Undergoing Sex Reassignment Surgery: Cohort Study in Sweden

CONTEXT: The treatment for transsexualism is sex reassignment, including hormonal treatment and surgery aimed at making the person's body as congruent with the opposite sex as possible. There is a dearth of long term, follow-up studies after sex reassignment. OBJECTIVE: To estimate mortality, morbidity, and criminal rate after surgical sex reassignment of transsexual persons. DESIGN: A population-based matched cohort study. SETTING: Sweden, 1973-2003. PARTICIPANTS: All 324 sex-reassigned persons (191 male-to-females, 133 female-to-males) in Sweden, 1973-2003. Random population controls (10:1) were matched by birth year and birth sex or reassigned (final) sex, respectively. MAIN OUTCOME MEASURES: Hazard ratios (HR) with 95% confidence intervals (CI) for mortality and psychiatric morbidity were obtained with Cox regression models, which were adjusted for immigrant status and psychiatric morbidity prior to sex reassignment (adjusted HR [aHR]). RESULTS: The overall mortality for sex-reassigned persons was higher during follow-up (aHR 2.8; 95% CI 1.8-4.3) than for controls of the same birth sex, particularly death from suicide (aHR 19.1; 95% CI 5.8-62.9). Sex-reassigned persons also had an increased risk for suicide attempts (aHR 4.9; 95% CI 2.9-8.5) and psychiatric inpatient care (aHR 2.8; 95% CI 2.0-3.9). Comparisons with controls matched on reassigned sex yielded similar results. Female-to-males, but not male-to-females, had a higher risk for criminal convictions than their respective birth sex controls. CONCLUSIONS: Persons with transsexualism, after sex reassignment, have considerably higher risks for mortality, suicidal behaviour, and psychiatric morbidity than the general population. Our findings suggest that sex reassignment, although alleviating gender dysphoria, may not suffice as treatment for transsexualism, and should inspire improved psychiatric and somatic care after sex reassignment for this patient group

NK-cell and T-cell functions in patients with breast cancer: effects of surgery and adjuvant chemo- and radiotherapy

Breast cancer is globally the most common malignancy in women. Her2-targeted monoclonal antibodies are established treatment modalities, and vaccines are in late-stage clinical testing in patients with breast cancer and known to promote tumour-killing through mechanisms like antibody-dependent cellular cytotoxicity. It is therefore increasingly important to study immunological consequences of conventional treatment strategies. In this study, functional tests and four-colour flow cytometry were used to detect natural killer (NK)-cell functions and receptors as well as T-cell signal transduction molecules and intracellular cytokines in preoperative breast cancer patients, and patients who had received adjuvant radiotherapy or adjuvant combined chemo-radiotherapy as well as in age-matched healthy controls. The absolute number of NK cells, the density of NK receptors as well as in vitro quantitation of functional NK cytotoxicity were significantly higher in preoperative patients than the post-treatments group and controls. A similar pattern was seen with regard to T-cell signalling molecules, and preoperative patients produced significantly higher amounts of cytokines in NK and T cells compared to other groups. The results indicate that functions of NK and T cells are well preserved before surgery but decrease following adjuvant therapy, which may speak in favour of early rather than late use of immunotherapeutic agents such as trastuzumab that may depend on intact immune effector functions

Pharmacokinetic studies on cladribine

The aims of the present study were to delineate the pharmacokinetics, in plasma and leukaemia cells, of cladribine (M), and to describe factors influencing the outcome of administration of CdA in order to individualize and optimize treatment. CdA is a nucleoside analogue with a cytotoxic activity in low-grade lymphoproliferative disorders and childhood acute myelogenous leukaemia. In addition, it has an immunomodulating effect used in multiple sclerosis. CdA is unstable at low pH and is deglycosylated by bacterial nucleoside phosphorylases. CdA can also be cleaved, in an enzymatic reaction in the presence of the hepatic enzyme methylthioadenosine phosphorylase, to the main metabolite 2chloroadenine (CAde). A more stable fluorinated analogue of CdA has been developed, 2-chloro-2'-arabio-fluoro-2'- deoxyadenosine (CAFdA). A reversed-phase high-performance liquid chromatographic method was developed for analyses of CdA, CAde and CAFdA. To minimize degradation before analysis, samples should be kept cold and not stored for more than 10 weeks. In a study Of 17 patients with leukaemia, we found large interpatient variability in both pharmacokinetic variables and a four-fold difference in activating enzyme activity. No clear correlations were seen between the plasma levels of CdA and the intracellular concentration of the active triphosphate, or to the response of treatment. The half-life was to some degree shorter for intracellular CdA-phosphates compared to CdA in plasma. In another study including 53 patients, we found no correlation between the the activity of the activating enzymes and the antiproliferative activity of CdA or the intracellular nucleotide levels of CdA in vitro. However, there was a large interindividual variability in enzyme activity and cytotoxicity. In a retrospective study consisting of 163 patients with different diagnoses, receiving different doses of CdA, administered by four different routes, using different treatment schedules, leaving different numbers of blood samples at different times, we used non- linear mixed effect modelling for the pharmaco-kinetic evaluation. For patients in the population with a mean weight of 73 kg, the clearance was 35 L/h with interindividual variability of 49% and half-life was estimated to be 17 hours. The oral bioavailability was 33% but the vari-ability after oral treatment was not increased compared with the variability after intravenous infusion. Individualized dosing on bases of BSA or weight is in this study not superior to administer all patients a fixed dose. The metabolite CAde has a lower cytotoxic effect than CdA, but may contribute to the cytotoxicity after oral administration, since 5 times more CAde was formed after oral treatment than after iv infusion (n=31 patients) and protein-binding of CAde is twice that of CdA. In conclusion, CdA can, by preference, be orally administered if the dose is adjusted for bioavailability and cytotoxicity of the metabolite, CAde

Utveckling av en regelkompatibel, patientsäker och användarvänlig webbapplikation för utskrift av läkemedelsetikketter med Zebraskrivare i pediatrisk vårdmiljö

In pediatric healthcare, accurate and efficient medication labeling for prepared medicines is crucial for patient safety. This thesis explores the development of a compliant, patient-safe, and user-friendly web application designed to print medication labels using Zebra printers. The primary objective is to address inefficiencies associated with current external labeling systems by providing an integrated, in-house solution that leverages existing hardware. The study involved qualitative research methods, including semi-structured interviews with healthcare professionals, a literature review, and a validated survey to assess the usability and patient safety of the application. The Agile Development Methodology was adopted to facilitate iterative development and continuous feedback integration. The resulting proof-of-concept web application enables healthcare professionals to generate and print medication labels using information from ePed, aiming to comply with Swedish regulations for NMIs (National Medical Information Systems) in design aspects. Other regulatory aspects were investigated separately. The application was designed with existing workflows in mind, and its user-friendliness, patient safety, and adherence to legal standards were evaluated. The application was well-received for its user-friendliness, but several improvements were identified to ensure it fully meets the needs of healthcare professionals and maintains the highest standards of patient safety and efficiency in pediatric care settings. The application was found to accurately find, print, and open ePed instructions. This thesis provides a foundational framework for developing a medication labeling system in pediatric care, offering potential benefits in terms of enabling in-house solutions and enhancing patient safety.Inom pediatrisk sjukvård är korrekt och effektiv märkning av iordningställda läkemedel avgörande för patientsäkerhet. Denna kandidatuppsats undersöker utvecklingen av en regelkompatibel, patientsäker och användarvänlig webbapplikation för att skriva ut läkemedelsetiketter med Zebraskrivare. Huvudmålet är att adressera ineffektiviteter i samband med nuvarande externa etikettsystem genom att tillhandahålla en integrerad intern lösning som utnyttjar befintlig hårdvara. Studien använde kvalitativa forskningsmetoder, inklusive semistrukturerade intervjuer med vårdpersonal, en litteraturstudie och en validerad enkät för att bedöma applikationens användbarhet och patientsäkerhet. Agil utvecklingsmetodik användes för att möjliggöra iterativ utveckling och kontinuerlig integration av feedback. Den resulterande proof-of-concept webbapplikationen gör det möjligt för vårdpersonal att generera och skriva ut läkemedelsetiketter med information från ePed, med målet att följa svenska regler för NMI (Nationella medicinska informationssystem) när det gäller designaspekter. Andra regulatoriska aspekter undersöktes separat. Applikationen designades med befintliga arbetsflöden i åtanke, och dess användarvänlighet, patientsäkerhet och efterlevnad av lagstadgade standarder utvärderades. Applikationen mottogs väl för sin användarvänlighet, men flera förbättringar identifierades för att säkerställa att den fullt ut möter vårdpersonalens behov och upprätthåller högsta standarder för patientsäkerhet och effektivitet inom pediatriken. Applikationen visade sig korrekt kunna hitta, skriva ut och öppna instruktioner från ePed. Denna kandidatuppsats ger en grund för att utveckla ett system för märkning av läkemedel inom pediatriken, med potentiella fördelar när det gäller att möjliggöra interna lösningar och förbättra patientsäkerheten

Nya Karolinska och det nya Infusionspumpssystemet

In November 2016 a brand new and highly technological hospital called New Karolinska Solna opened in Stockholm. In connection with the planning of the hospital, new medical devices were procured, including a new infusion system that is now in use. Previously, each ward at the hospital had their own pumps and was responsible for updates and maintenance. Now, the hospital will instead have a floating pump system, which means that the hospital will own the pumps. The infusion pumps will be floating between the wards without being linked to a specific ward or department. The updates that were previously done when the need arose at the ward will now be a common process for the entire hospital. The aim of the project was to develop new guidelines for how the update process should be done on New Karolinska Solna's new infusion pump system. Through interviews with key personnel during the procurement process, the medical technicians department and caseworkers, new guidelines have been written, given the already existing technical conditions. During the course of the project it has been found that there are major shortcomings of information and communication within the hospital. The guidelines presented in the result are an important part to ensure that information related to the update comes to the caregivers at New Karolinska Solna, thus simplifying and streamlining the update of the infusion pumps