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Background: Tamoxifen is a widely prescribed selective estrogen receptor modulator (SERM) used for the treatment and prevention of hormone receptor positive breast cancer. While tamoxifen has proven effective in lowering the chance of cancer recurrence, current data point to a possible link between tamoxifen treatment and unfavorable psychological consequences. Objective: In this study, the World Health Organization (WHO) pharmacovigilance database will be analyzed to determine the frequency and kind of psychiatric disorders linked to the use of the tamoxifen as well as Kosovo pharmacists’ awareness of these reported adverse effects. Methods: The WHO pharmacovigilance database, VigiBase, was queried for adverse drug reaction reports related to tamoxifen use between 1978 and 2022. A cross-sectional survey of 70 community pharmacies operating in Kosovo was conducted as part of the data collection between January 1 and March 1, 2023, with the goal of comparison. Results: The search of VigiBase yielded a total of 1746 reported cases of psychiatric disorders. The data were further classified based on the type of psychiatric adverse effect, including depressive disorders, anxiety disorders, cognitive impairment, and other psychiatric symptoms. Depressive disorders were the most frequently reported adverse event, accounting for 30% of the cases. Anxiety disorders and sleeps disorders were also prevalent, comprising 11% and 7% of the reported cases, respectively. Other psychiatric symptoms such as mood swings, insomnia, and confusion were observed in 32% of the cases. In Kosovo, 30% of pharmacist’s linked tamoxifen with depression, 25% with anxiety, 56% with sleep disorders, 53% insomnia, and 18% confusion. Conclusions: Based on the WHO pharmacovigilance database and knowledge of Kosovo pharmacists for these documented adverse effects, this study analyzes tamoxifen-induced psychiatric disorders. The findings show how attentive healthcare professionals must be to any potenti

Vaccination is an effective way to control many infectious diseases in fish. Israeli fish farming has successfully used two vaccines over the last 30 years and has no problem with the side effects of vaccination. However, after introducing new species, a new problem emerged: these fish, after vaccination, demonstrated peritoneal lesions such as granulomas. At the same time, the fish did not show retarded growth or suffering during the fattening period. This study was conducted to establish the connection between vaccination and the appearance of granulomas. Evidence drawn from this research work and comparing vaccinated and non-vaccinated fish confirms that intraperitoneal granulomas do not impact the growth, performance, or fish fillet quality at harvest.

[Resumen] Introducción: Las mujeres con cáncer de mama a tratamiento con quimioterapia presentan una serie de síntomas, tanto físicos como emocionales, que obstaculizan su bienestar. El creciente interés en terapias complementarias ha ofrecido nuevas vías para mejorar la calidad de vida y el autocuidado de los pacientes en numerosas enfermedades. Este aumento en la demanda resalta la necesidad de que los profesionales sanitarios reciban formación adecuada y ofrezcan un buen asesoramiento a los pacientes. Objetivos: Evaluar la evidencia actual sobre la eficacia de las terapias complementarias para controlar los efectos secundarios de la quimioterapia y mejorar la calidad de vida, así como proponer intervenciones de enfermería para asesorar a las pacientes interesadas en estas terapias. Metodología: Revisión bibliográfica de la literatura científica publicada en los últimos dos años, utilizando criterios específicos de inclusión y exclusión. Resultados: Tras el filtrado, se obtiene un total de 11 artículos para su posterior revisión. Discusión y conclusiones: El uso de terapias complementarias en pacientes con cáncer de mama ha experimentado un notable aumento e interés. Terapias como el yoga, la acupuntura, la meditación y los extractos herbarios han demostrado mejoras significativas en la reducción de síntomas físicos y emocionales asociados con la quimioterapia, además de incrementar la calidad de vida y el autocuidado. Es esencial, desde el punto de vista enfermero, obtener formación en evidencia científica sólida y asesorar correctamente a los pacientes., [Resumo] Introdución: As mulleres con cancro de mama que se someten a quimioterapia presentan unha serie de síntomas, tanto físicos como emocionais, que dificultan o seu benestar. O crecente interese polas terapias complementarias ofreceu novas vías para mellorar a calidade de vida e o autocoidado dos pacientes en numerosas enfermidades. Este aumento da demanda pon de manifesto a necesidade de que os profesionais sanitarios reciban unha formación adecuada e proporcionen un bo asesoramento aos pacientes. Obxectivos: Avaliar a evidencia actual sobre a eficacia das terapias complementarias para controlar os efectos secundarios da quimioterapia e mellorar a calidade de vida, así como propoñer intervencións de enfermería para asesorar aos pacientes interesados nestas terapias. Metodoloxía: Revisión bibliográfica da literatura científica publicada nos últimos dous anos, utilizando criterios específicos de inclusión e exclusión. Resultados: despois do filtrado, obtéñense un total de 11 artigos para a súa posterior revisión. Discusión e conclusións: O uso de terapias complementarias en pacientes con cancro de mama experimentou un notable incremento e interese. As terapias como o ioga, a acupuntura, a meditación e os extractos de herbas mostraron melloras significativas na redución dos síntomas físicos e emocionais asociados á quimioterapia, así como no aumento da calidade de vida e do coidado persoal. É fundamental, dende o punto de vista de enfermaría, obter formación en evidencia científica sólida e asesorar correctamente aos pacientes., [Abstract] Introduction: Women with breast cancer undergoing chemotherapy treatment present with a range of symptoms, both physical and emotional, that hinder their well-being. The growing interest in complementary therapies has offered new avenues to improve the quality of life and self-care of patients with numerous diseases. This increase in demand highlights the need for healthcare professionals to receive adequate training and provide good advice to patients. Objectives: To evaluate the current evidence on the efficacy of complementary therapies to control the side effects of chemotherapy and improve quality of life, as well as to propose nursing interventions to counsel patients interested in these therapies. Methodology: Bibliographic review of the scientific literature published in the last two years, using specific inclusion and exclusion criteria. Results: After filtering, a total of 11 articles were obtained for subsequent review. Discussion and conclusions: The use of complementary therapies in breast cancer patients has experienced a remarkable increase and interest. Therapies such as yoga, acupuncture, meditation and herbal extracts have shown significant improvements in the reduction of physical and emotional symptoms associated with chemotherapy, in addition to increasing quality of life and self-care. It is essential, from a nursing point of view, to obtain training in sound scientific evidence and to counsel patients correctly.

Einleitung: Stress und Stressfolgeerscheinungen stellen in unserer Gesellschaft ein stetig zunehmendes Problem dar. Dies gilt insbesondere für Studierende. Aufgrund der guten Evidenz für die Wirksamkeit der Lichttherapie zur (adjuvanten) Behandlung von affektiven Störungen soll in der vorliegenden Studie erstmals der Einsatz einer morgendlichen, mehrwöchigen Lichttherapie bei Studierenden unter hoher Stressbelastung evaluiert werden. Methoden: Insgesamt wurden 83 Studierende aus den Studienfächern Medizin, Pharmazie und Jura drei Wochen vor einer großen Prüfung in diese Studie eingeschlossen und über diese drei Wochen täglich, einstündig, unmittelbar nach dem morgendlichen Erwachen entweder tageslicht-weißem, hellen Interventionslicht (5.300 Kelvin; 5.000 Lux am Auge) oder rötlichem, gedimmten Placebo-Licht (2.200 Kelvin; 100 Lux am Auge) exponiert. Zur Erfassung möglicher Lichtwirkungen wurden subjektive Parameter (Stress, Stimmung, Depression, somatische Symptome, Angst, subjektive Schlafqualität und Nebenwirkungen) mit einer Smartphone-App erhoben. Weiters wurde ein spezifischer kognitiver Test freitags, jeweils unmittelbar vor und nach der Lichtexposition, durchgeführt. Die objektive Schlafqualität und die Ruhe-Aktivitätsrhythmik wurden anhand eines kontinuierlich am Handgelenk getragenen Aktimeters erfasst. Die genannten Messgrößen wurden erhoben, um potentielle Lichtwirkungen auf drei zeitlichen Ebenen erfassen zu können: (1) die kumulative Lichtwirkung über drei Wochen, (2) tägliche und wöchentliche Lichteffekte und (3) unmittelbare Wirkungen jeder Lichtexposition. Ergebnisse: Die Ergebnisse zeigten, dass eine dreiwöchige Exposition mit hellem Interventionslicht im Vergleich zum gedimmten Placebo-Licht bei stark gestressten Studierenden die subjektiven Anforderungsgefühle reduzierte und die erlebte Selbstwirksamkeit signifikant erhöhte. Das unmittelbare Angsterleben wurde durch die Nutzung der hellen Lichtintervention signifikant reduziert. Des Weiteren zeigt, Introduction: Stress and the consequences of stress are an increasing problem in our society. This is particularly true for students. Due to the good evidence for the effectiveness of light therapy for the (adjuvant) treatment of affective disorders, this study is the first to evaluate the use of morning light therapy over several weeks in students with high stress levels. Methods: A total of 83 students from the fields of medicine, pharmacy and law were included in this study. Three weeks before a major exam, they were exposed to either a daylight-white, bright light intervention (5,300 Kelvin; 5,000 lux at eye level) or a reddish, dimmed placebo light (2,200 Kelvin; 100 lux at eye level) every day for one hour, immediately after waking up in the morning. To evaluate possible light effects, subjective parameters (stress, mood, depression, somatic symptoms, anxiety, subjective sleep quality and side effects) were measured using a smartphone app. In addition, a specific cognitive test was carried out on Fridays, immediately before and after exposure to light. Objective sleep quality and rest-activity rhythms were measured using an actimeter worn continuously on the wrist. The mentioned measured variables were collected in order to evaluate potential light effects on three temporal levels: (1) the cumulative light effect over three weeks; (2) daily and weekly light effects; and (3) immediate effects of each light exposure. Results: The results showed that a three-week exposure to a bright light intervention reduced subjective feelings of demand and significantly increased perceived self-efficacy in highly stressed students compared to dimmed placebo light. The immediate experience of anxiety was significantly reduced by the use of the bright light intervention. Furthermore, the bright light intervention showed a trend towards a significant reduction in the overall depression experience. After three weeks of light exposure, independently of the light condition, there w, vorgelegt von Benjamin Stampfer, MSc., MSc., in englischer Sprache, Dissertation Universität Innsbruck 2024

Background Daylight photodynamic therapy (dPDT) and topical 5-fluorouracil (5-FU) are each effective treatments for thin grade I actinic keratosis (AKs), but less so for thicker grade II-III AKs. Prolonged topical treatment regimens can be associated with severe skin reactions and low compliance. This study compares the efficacy of sequential 4 % 5-FU and dPDT with dPDT monotherapy for multiple actinic keratoses. Methods Sixty patients with a total of 1547 AKs (grade I: 1278; grade II: 246; grade III: 23) were treated in two symmetrical areas (mean size 75 cm2) of the face or scalp, which were randomized to (i) 4% 5-FU creme twice daily for 7 days before a single dPDT procedure and (ii) dPDT monotherapy. Daylight exposure was either outdoor or indoor daylight. Results Twelve weeks after treatment 87 % of all AKs cleared after 5-FU+dPDT compared to 74 % after dPDT alone (p<0.0001). For grade II AKs, the lesion response rate increased from 55 % with dPDT monotherapy to 79 % after 5-FU+dPDT (p<0.0056). Moderate/severe erythema was seen in 88 % 5-FU+dPDT areas compared to 41 % of dPDT areas two days after dPDT. Twelve weeks after treatment 75 % of the patients were very satisfied with both treatments. Conclusions Sequential 5-FU and dPDT was more effective than dPDT monotherapy in the treatment of AKs, especially for grade II AKs. Local skin reactions were more pronounced after combination treatment, but no patients discontinued the treatment. The combination of 5-FU and dPDT is an effective treatment of large treatment areas with high compliance and satisfaction., Background: Daylight photodynamic therapy (dPDT) and topical 5-fluorouracil (5-FU) are each effective treatments for thin grade I actinic keratosis (AKs), but less so for thicker grade II-III AKs. Prolonged topical treatment regimens can be associated with severe skin reactions and low compliance. This study compares the efficacy of sequential 4 % 5-FU and dPDT with dPDT monotherapy for multiple actinic keratoses. Methods: Sixty patients with a total of 1547 AKs (grade I: 1278; grade II: 246; grade III: 23) were treated in two symmetrical areas (mean size 75 cm2) of the face or scalp, which were randomized to (i) 4% 5-FU creme twice daily for 7 days before a single dPDT procedure and (ii) dPDT monotherapy. Daylight exposure was either outdoor or indoor daylight. Results: Twelve weeks after treatment 87 % of all AKs cleared after 5-FU+dPDT compared to 74 % after dPDT alone (p<0.0001). For grade II AKs, the lesion response rate increased from 55 % with dPDT monotherapy to 79 % after 5-FU+dPDT (p<0.0056). Moderate/severe erythema was seen in 88 % 5-FU+dPDT areas compared to 41 % of dPDT areas two days after dPDT. Twelve weeks after treatment 75 % of the patients were very satisfied with both treatments. Conclusions: Sequential 5-FU and dPDT was more effective than dPDT monotherapy in the treatment of AKs, especially for grade II AKs. Local skin reactions were more pronounced after combination treatment, but no patients discontinued the treatment. The combination of 5-FU and dPDT is an effective treatment of large treatment areas with high compliance and satisfaction.

Background Topical corticosteroids (TCS) are used to treat most patients with chronic hand eczema (CHE), but knowledge about TCS-related adverse events in CHE is limited. Objectives To investigate patient-reported adverse events to TCS in CHE patients. Methods Data on adverse events related to TCS use in patients with CHE were analyzed from the Danish Skin Cohort; a prospective survey of a hospital cohort. We assessed patients’ knowledge about TCS use and adverse event risks, and preference of TCS versus a nonsteroidal topical alternative. Results Of 724 adults with CHE (64.0% women; mean age 57.5 [standard deviation 12.8] years), 64.1% reported skin atrophy, 41.4% cracks/fissures, 23.9% bleeding, 45.9% pain/stinging sensation, 40.0% reduced hand dexterity, and 40.2% worsening of CHE signs or symptoms from using TCS. We observed CHE-severity-dependent associations (all groups; P < .0001). Most patients (76.4%) would prefer a nonsteroidal option, 10.9% were neutral/indifferent, and 12.7% would prefer TCS for CHE. The median numerical rating scale-score (ranging from 0 to 10) was 10 (interquartile range 6-10) for preferring a nonsteroidal topical treatment. Limitations Differences across TCS formulations were unexplored. Conclusion TCS-related cutaneous adverse events were common. There is a desire from patients for novel steroid-free topical alternatives for CHE treatment., Background: Topical corticosteroids (TCS) are used to treat most patients with chronic hand eczema (CHE), but knowledge about TCS-related adverse events in CHE is limited. Objectives: To investigate patient-reported adverse events to TCS in CHE patients. Methods: Data on adverse events related to TCS use in patients with CHE were analyzed from the Danish Skin Cohort; a prospective survey of a hospital cohort. We assessed patients’ knowledge about TCS use and adverse event risks, and preference of TCS versus a nonsteroidal topical alternative. Results: Of 724 adults with CHE (64.0% women; mean age 57.5 [standard deviation 12.8] years), 64.1% reported skin atrophy, 41.4% cracks/fissures, 23.9% bleeding, 45.9% pain/stinging sensation, 40.0% reduced hand dexterity, and 40.2% worsening of CHE signs or symptoms from using TCS. We observed CHE-severity-dependent associations (all groups; P <.0001). Most patients (76.4%) would prefer a nonsteroidal option, 10.9% were neutral/indifferent, and 12.7% would prefer TCS for CHE. The median numerical rating scale-score (ranging from 0 to 10) was 10 (interquartile range 6-10) for preferring a nonsteroidal topical treatment. Limitations: Differences across TCS formulations were unexplored. Conclusion: TCS-related cutaneous adverse events were common. There is a desire from patients for novel steroid-free topical alternatives for CHE treatment.

Tres artículos científicos conforman la presente tesis doctoral, titulada “Factores relacionados con la calidad de vida, la depresión, la ansiedad, la imagen corporal y la autoestima, en mujeres mastectomizadas supervivientes de cáncer de mama”, que sigue la modalidad por compendio de publicaciones. El cáncer de mama no solo es el cáncer más común entre las mujeres, sino que también es aquel que mayor tratamiento exige, derivando unos efectos secundarios de larga duración afectando varios aspectos de la calidad de vida de la paciente, como son las capacidades físicas y mentales. Con el objetivo principal de identificar los factores asociados a la calidad de vida, la depresión, la ansiedad, la imagen corporal y la autoestima, se realizaron tres artículos descriptivos a través de una muestra de 198 mujeres supervivientes de cáncer de mama, donde se estudiaron las variables edad, tipo de cirugía, si estaban recibiendo tratamiento durante la evaluación, el nivel de estudios, el estado civil, si tenían trabajo o no durante el diagnóstico y el tratamiento, el tiempo trascurrido desde el diagnóstico hasta la evaluación, si habían sido sometidas a una reconstrucción de mama, si tenían antecedentes familiares de primer grado, si habían recibido apoyo psicológico durante el transcurso de la enfermedad, si tenían sentido del humor y por último el grado de conocimiento que disponían sobre el diagnóstico, tratamiento y pronóstico de la enfermedad. En lo relacionado a la calidad de vida, la edad, el tipo de cirugía y el tiempo trascurrido desde el diagnóstico hasta la evaluación de la calidad de vida son factores asociados a la misma, donde las mujeres más jóvenes señalan una mayor sintomatología, el ser intervenida de una cirugía conservadora no indica una mejor calidad de vida y a más tiempo trascurrido desde el diagnóstico indica una mayor puntuación de salud general, una mejor funcionalidad, pero no por ello una menor sintomatología. En cuanto a la depresión y ansiedad, el no, Three scientific articles make up the present doctoral thesis, entitled "Factors related to quality of life, depression, anxiety, body image and self-esteem, in mastectomized women breast cancer survivors", which follows the publication compendium modality. Breast cancer is not only the most common cancer among women, but also the one that requires the most treatment, resulting in long-lasting side effects affecting several aspects of the patient's quality of life, such as physical and mental abilities. With the main objective of identifying the factors associated with quality of life, depression, anxiety, body image and self-esteem, three descriptive articles were carried out on a sample of 198 women survivors of breast cancer, where the variables studied were age, type of surgery, whether they were receiving treatment during the evaluation, level of education, marital status, whether or not they were employed during diagnosis and treatment, the time elapsed from diagnosis to evaluation, whether they had undergone breast reconstruction, whether they had a first-degree family history, whether they had received psychological support during the course of the disease, whether they had a sense of humor, and finally the degree of knowledge they had about the diagnosis, treatment and prognosis of the disease. In relation to quality of life, age, type of surgery and time elapsed from diagnosis to quality of life assessment are factors associated with quality of life, where younger women report greater symptomatology, conservative surgery does not indicate a better quality of life and the more time elapsed since diagnosis indicates a higher general healthcare score, better functionality, but not less symptomatology. As for depression and anxiety, not having a partner, being receiving treatment during the evaluation, having undergone mastectomy surgery and having a job are factors associated with greater symptoms of depression and anxiety, where the prevalence of these sympt

Background: Virtual Reality (VR) uses computer technology to create a simulated environment. VR is a growing technology with promising extensive applications in different areas such as Medicine, entertainment, sports, gaming, and simulation. However, information about VR side effects is still limited. We aimed to identify the most frequent physical side effects caused by VR therapeutic applications. Methodology: All available full-text articles evaluating VR as a therapeutic intervention and side effects using the Simulator Sickness Questionnaire (SSQ) between 2016 and 2021 were consulted across 4 electronic (Entrez Pubmed, Scopus, Science Direct, and Wiley databases). The methodological quality was assessed using the PEDro scale. Results: Ten out of 55 reviewed articles (18%) met inclusion/exclusion criteria, including a sample of 416 patients, mean age of 24.54 (15—52.6) years old. According to the PEDro scale, two articles (20%) were considered good or excellent. Side effects were reported more frequently with head-mounted displays compared to desktop systems, especially disorientation, followed by nausea and oculomotor disturbances. Conclusions: Although VR might have positive effects as a therapeutic tool, VR can also cause side events. As in any othertherapeutic intervention, itis importantto understand the effectiveness and safety before planning a VR intervention using a well-designed scientific methodology., Antecedentes: La Realidad Virtual (RV) proporciona un entorno simulado mediante el uso de tecnologías informáticas. Aunque la RV es una tecnología en expansión con aplicaciones prometedoras en diferentes áreas de la medicina, ocio, deportes, juegos y simulaciones, todavía existe poca información sobre su seguridad. El objetivo de este estudio es identificar los efectos secundarios más frecuentes provocados por las aplicaciones terapéuticas de la RV. Metodología: Se consultaron todos los artículos de texto completo disponibles que evaluaron la RV como intervención terapéutica y sus efectos secundarios utilizando el Simulator Sickness Questionnaire (SSQ), entre 2016 y 2021, en 4 bases electrónicas: Entrez Pubmed, Scopus, Science Direct y bases de datos Wiley. La calidad metodológica se evaluó usando la escala PEDro. Resultados: Diez de los 55 artículos revisados (18%) cumplieron con los criterios de inclusión/exclusión, incluyendo una muestra total de 416 pacientes, edad media de 24,54 anos ˜ (15—52,6 anos). ˜ Dos artículos (20%) fueron considerados buenos o excelentes. Los efectos secundarios asociados a la RV más frecuentes fueron desorientación, náauseas y trastornos oculomotores, especialmente cuando se usaban con «head-mounted displays» comparados con las pantallas del ordenador/TV. Conclusiones: Aunque la RV se usa cada vez más en diferentes intervenciones terapéuticas, la RV puede producir efectos secundarios. Para planificar una intervención terapéutica a través de RV, es importante conocer su seguridad y eficacia a través de estudios con una metodología científica adecuada., The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was co-financed by the Erasmus+ program of the European Union through the 2018-1-ES01-KA201-050659 project.

Recent years have seen major developments in psychotherapy research that suggest the need to address critical methodological issues. These recommendations, developed by an international group of researchers, do not replace those for randomized controlled trials, but rather supplement strategies that need to be taken into account when considering psychological treatments. The limitations of traditional taxonomy and assessment methods are outlined, with suggestions for consideration of staging methods. Active psychotherapy control groups are recommended, and adaptive and dismantling study designs offer important opportunities. The treatments that are used, and particularly their specific ingredients, need to be described in detail for both the experimental and the control groups. Assessment should be performed blind before and after treatment and at long-term follow-up. A combination of observer- and self-rated measures is recommended. Side effects of psychotherapy should be evaluated using appropriate methods. Finally, the number of participants who deteriorate after treatment should be noted according to the methods that were used to define response or remission., Depto. de Personalidad, Evaluación y Psicología Clínica, Fac. de Psicología, TRUE, pub

Introduction: Preventing side effects is important to ensure optimal psychopharmacotherapy and therapeutic adherence among psychiatric patients. Obtaining the pharmacogenetic profile of CYP2C19 and CYP2D6 can play an important role in this. When the genotype-predicted phenotype shifts because of the use of co-medication, this is called phenoconversion. The aim was to study the influence of the pharmacogenetic (PGx) profile and phenoconversion on side effects experienced by psychiatric patients. Methods: A retrospective cohort study was performed using data from 117 patients from a psychiatric outpatient clinic. Patients were genotyped with a psychiatric PGx panel and side effects were evaluated using the Udvalg for Kliniske Undersølgelser side effects rating scale (UKU). Results: Of all patients, 10.3% and 9.4% underwent phenoconversion (any shift in predicted phenotype) for CYP2C19 and CYP2D6 respectively. No significant associations were found between the phenotype and UKU-score. 75% of the patients with an Intermediate metabolizer (IM) or Poor metabolizer (PM) phenoconverted phenotype of CYP2C19 experienced nausea and vomiting compared to 9.1% of the Normal metabolizer (NM) and Ultrarapid metabolizer (UM) patients (p = 0.033). 64% of the patients with an IM or PM phenoconverted phenotype of CYP2D6 experienced the side effect depression compared to 30.4% NMs and UMs (p = 0.020). CYP2D6 IM and PM patients had a higher concentration-dose ratio than NM patients (p < 0.05). Discussion: This study underlines the importance to consider phenoconversion when looking at a patient's genotype. This is important for a better prediction of the phenotype and preventing possible side effects under a specific psychopharmacotherapy.

Cerebral palsy (CP) is a heterogeneous group of neurological disorders caused by fetal or infant brain damage that often involves deficits in upper limb (UL) posture and function. Knowledge about effective methods of assessment and treatment of UL in CP is not extensive. In this thesis, different aspects of these two are explored. In Paper I we retrospectively investigated the effect of a long-term treatment regime developed in Västerbotten county habilitation service. The treatment regime included intramuscular injections of botulinum toxin type A (BoNT-A) combined with occupational therapy (OT) and movement training. The results of passive extension of the wrist with fingers extended and the assessment of hand function in children with severe hand function impairment (initially House functional classification 0-1) were analyzed over time. Twenty-five children were divided into 3 groups depending on the treatment regime start age (before or after the age of 7) and treatment regime availability. We found significantly worse passive extension of the wrist with fingers extended in children who did not have a chance to benefit from therapy in early childhood. Additionally, an improvement in the passive movement of the wrists was noted in children who completed the treatment regime before the age of 7. Regarding hand function, a significant difference was found between children who received treatment in early childhood and those who received treatment as adolescents. The injections of BoNT-A in CP are common, however the monitoring of eventual side effects and adverse events (AEs) after this treatment is difficult to perform in clinical practice. To facilitate this process, we created a new, no previously validated questionnaire (Paper II). The questionnaire was given to patients or their caregivers to be completed after each BoNT-A treatment. 94% of participants returned the questionnaire. 80 % were filled in completely which proves the effectiveness of the applied fo

IntroductionWhile phosphodiesterase type 5 inhibitors (PDE5is) and others are used to treat Erectile dysfunction (ED), many patients are either unresponsive or resistant to it. Stem cell therapy (SCT) is a promising alternative approach. Numerous preclinical trials have demonstrated improved erectile function in animal models using SCT, although the number of clinical trials investigating SCT for men with ED is limited. Nonetheless, findings from human clinical trials suggest that SCT may be a useful treatment option.Areas coveredBiomedical literature, including PubMed, ClinicalTrials.gov, and European Union Clinical Trials Registry, were analyzed to summarize and synthesize information on stem cell therapy for ED in this narrative review. The achievements in preclinical and clinical evaluations are presented and critically analyzed.Expert opinionSCT has demonstrated some benefits in improving erectile function, while further studies are urgently needed. Such studies would provide valuable insights into the optimal use of stem cell therapy and its potential as a therapeutic option for ED. Taking advantage of different mechanisms of action involved in various regenerative therapies, combination therapies such as SCT and low-energy shock waves or platelet-rich plasma may provide a more effective therapy and warrant further research.

Background: Breast cancer is the most common type of cancer among women. A range of treatments are offered, all of which have side effects. Previous research has shown that women suffer from various side effects associated with breast cancer treatment. Knowledge of the women's experiences is needed, to provide support and good care. Aim: The aim of this study was to describe women’s experiences of side effects caused by breast cancer treatment. Method: This literature-based study was based on qualitative research. Friberg's five-step model was used in the analysis of the study. Eleven articles were analysed. Results: Four themes and eleven subthemes were identified. Themes that emerged were A different body, Different everyday life, Adherence to treatment and The need for knowledge and to be seen. A different body describes bodily-, sexual-, and cognitive changes. Different everyday lifedescribes how the women´s daily lives are limited by the different side effects. Adherence to treatment highlights emotions and how the emotions affected the women´s adherence to breast cancer treatment and The need for knowledge and to be seen describes experiences of lack of information and support. Conclusion: Women experience several challenges during breast cancer treatment. By having a holistic perspective and conducting person centred care, side effects can become more manageable, and women's suffering can be alleviated.

Bakgrund. En effektiv behandling för hiv kom år 1996. Behandlingen för hiv kan orsaka en rad biverkningar som skulle kunna påverka följsamheten. Minskad följsamhet har lett till läkemedelsresistens. Syfte. Syftet är att undersöka upplevelser av följsamhet hos personer som lever med hiv under antiretroviral tablettbehandling (ART). Metod. En litteraturstudie med kvalitativ ansats. Resultat. 12 vetenskapliga artiklar ligger till grund för litteraturstudiens resultat. Majoriteten av personer som lever med hiv (PLH) hittade egna strategier för att hitta motivation till att uppnå följsamhet. Depressiva symtom och substansberoende var i flertalet fall en hindrande faktor för PLH:s följsamhet. PLH:s omgivning och nätverk var både en motverkande faktor och en hjälpsam faktor för PLH:s följsamhet. För PLH, som inte hade råd med mat eller som hade en instabil levnadssituation, upplevde svårigheter med att uppnå följsamhet. Hur PLH kände sig bemötta av vårdgivare påverkade följsamheten. För PLH var det viktigt för PLH att känna sig delaktiga i sin vård gällande ART och biverkningar. Hjälpmedel och patientutbildning var verktyg som kunde underlätta för PLH att uppnå följsamhet. Rutiner visade sig vara väsentligt för PLH att uppnå följsamhet. Slutligen var biverkningar till följd av ART en hindrande faktor för att uppnå följsamhet. Konklusion. Biverkningar, samsjuklighet med psykisk ohälsa samt stigma var de främsta faktorerna som hindrade PLH att uppnå följsamhet. Vidare kunskapsutveckling behövs för att minska biverkningar, behandla samsjuklighet och motarbeta stigmatisering för att PLH lättare ska upprätthålla följsamheten. Endel av kunskapsutvecklingen är att den grundutbildade sjuksköterskan behöver bredare kunskap., Background. The effective treatment for HIV was available in 1996. The treatment for HIV causes several side effects that could have an impact on adherence. Low adherence has led to medical resistance. Aim. The aim is to explore experiences of adherence by people living with HIV with ongoing antiretroviral pill treatment (ART). Method. A literature study with a qualitative approach. Result. This study is based on 12 scientific articles. The majority of people living with HIV (PLH) discovered their own strategies to find motivation in being adherent. Depressed mood and substance addiction were a hindering factor in being adherent. The network and surrounding of PLH were either a discouraging or facilitating factor to adherence. PLH with food insecurity and homelessness experienced difficulties adhering to ART. Clinicians approach to PLH influenced the rate of adherence. It was essential that PLH was involved in their own care regarding ART and side effects. Utilities and patient education were useful tools to facilitate adherence. Routines were shown to be essential for PLH in being adherent. Lastly, side effects due to ART were a hindering factor in achieving adherence. Conclusion. Side effects, comorbidity with mental illness and stigma were the main factors hindering PLH in achieving adherence. Further research is needed to reduce side effects, treat comorbidity and counteract stigma to facilitate adherence. The further research is needed to broaden the knowledge of registered nurses.

Development of drugs often fails due to toxicity and intolerable side effects. Recent advancements in the scientific community have rendered it possible to leverage machine learning techniques to predict individual side effects with domain knowledge features, such as drug classification. While several factors can be used to anticipate drug effects including their targets, pathways, and drug classes, it is unclear which domain knowledge is most predictive and whether certain domain knowledge is more important than others for different side effects. The goal of this project is to understand the predictive values of drug targets, drug classification (level 2 ATC codes), and protein-protein interaction networks (PathFX targets and network proteins) for the prediction of 30 frequently occurring side effects. We compared the prediction accuracy for individual side effects of trained models across five domain knowledge combinations and discovered that level 2 ATC codes have the highest predictive value across the domain knowledge features. Logistic regression coefficient analyses further suggest that side effects are significantly influenced by drug targets and drug classes, and not PathFX targets and network proteins. Our quantitative assessments may inform the development of safe and effective drugs by understanding the domain knowledge features underlying frequently occurring drug-induced side effects.

A recurrent condition that affects up to 10% of people worldwide is gastric ulceration illness. The existence of gastric juice pH with the lowering of mucous defences is prerequisites for the development of chronic ulcers. The main variables affecting the mucosa susceptibility to damage include Helicobacter pylori (H. pylori) infections or non-steroidal anti-inflammatory medicines (NSAIDs). Proton pump inhibitors (PPIs) including histamine-2 (H2) receptor inhibitors, two common therapies for peptic ulcers, have been linked to side impacts, recurrence or a variety of pharmacological combinations. Conversely, therapeutic herbs or the chemicals they contain may be used to cure or eliminate a wide range of illnesses. Therefore, prominent pharmaceutical herbs that can be utilised to cure or avoid ulcers in the intestines are presented in this research.

Clozapine is often underused due to concerns about adverse drug reactions (ADRs) but studies into their prevalences are inconclusive. We therefore comprehensively examined prevalences of clozapine-associated ADRs in individuals with schizophrenia and demographic and clinical factors associated with their occurrence. Data from a multi-center study (n = 698 participants) were collected. The mean number of ADRs during clozapine treatment was 4.8, with 2.4 % of participants reporting no ADRs. The most common ADRs were hypersalivation (74.6 %), weight gain (69.3 %), and increased sleep necessity (65.9 %), all of which were more common in younger participants. Participants with lower BMI prior to treatment were more likely to experience significant weight gain (>10 %). Constipation occurred more frequently with higher clozapine blood levels and doses. There were no differences in ADR prevalence rates between participants receiving clozapine monotherapy and polytherapy. These findings emphasize the high prevalence of clozapine-associated ADRs and highlight several demographic and clinical factors contributing to their occurrence. By understanding these factors, clinicians can better anticipate and manage clozapine-associated ADRs, leading to improved treatment outcomes and patient well-being

Tato bakalářská práce se zaměřuje na depresogenní účinek některých léčiv, zejména antihypertenziv a kardiovaskulárních léčiv, hormonálních kontraceptiv, kortikosteroidů, antiparkinsonik, analgetik a antimigrenik, antikonvulziv a antiepileptik, benzodiazepinů, antiulcerotik, protinádorových léčiv a antibiotik. Práce shrnuje mechanismy, jakými mohou tyto skupiny léčiv navozovat a zhoršovat depresivní symptomy., This bachelor's thesis focuses on the depressogenic effect of some drugs, especially antihypertensive and cardiovascular drugs, hormonal contraceptives, corticosteroids, antiparkinsonian drugs, analgesics and antimigraine drugs, anticonvulsants and antiepileptics, benzodiazepines, antiulcer drugs, antitumor drugs and antibiotics. This thesis summarizes the mechanisms by which these groups of drugs can induce and worsen depressive symptoms., Fakulta chemicko-technologická, 1. Prezentace výsledků bakalářské práce. 2. Diskuze k posudku vedoucího bakalářské práce. 3. Student/ka zodpověděl/a všechny dotazy a připomínky k bakalářské práci., Dokončená práce s úspěšnou obhajobou

Electrochemical energy storage technologies hold great significance in the progression of renewable energy. Within this specific field, flow batteries have emerged as a crucial component, with Zinc–Nickel single flow batteries attracting attention due to their cost-effectiveness, safety, stability, and high energy density. This comprehensive review aims to thoroughly evaluate the key concerns and obstacles associated with this type of battery, including polarization loss, hydrogen evolution reaction, and dendrite growth, among others. Additionally, the study highlights ongoing research endeavors focused on addressing these concerns, such as optimizing battery operating conditions and developing new electrodes. Furthermore, recent advancements in experimental processes and multi-scale numerical simulations of Zinc–Nickel single flow batteries, facilitated by the visual literature analysis software VOSviewer, are also explored. The primary objective of this review is to acquire a comprehensive understanding of the electrochemical reaction and internal mass transfer mechanism of Zinc–Nickel single flow batteries, while also anticipating future research directions and prospects.

Background: For many years triptans have been the cornerstone of acute migraine treatment. Nevertheless, treatment with triptans may not always be initiated due to contraindications (seen in approximately one fifth of patients) or inadequate response (seen in approximately one third of patients). New acute therapies, including 5-hydroxytryptamine (5-HT)1F receptor agonists, also known as ditans (lasmiditan) and small molecule antagonists of the calcitonin gene-related peptide receptor, also known as gepants (rimegepant and ubrogepant), may be an effective alternative. Methods: We searched Pubmed for keywords, summarized the literature and provided a comprehensive review on the place of next generation acute migraine specific treatments among triptans. Results and conclusion: Post-hoc analyses reported no differences in efficacy of gepants/ditans between responders and non-responders to triptans, but research is hampered by lack of consensus on the definition of non-responder. Due to (partially) overlapping mechanisms of action, it remains unknown whether combination therapy with lasmiditan, gepants and triptans will have added value over monotherapy. Preclinical studies and post-hoc analyses cautiously indicate that these new drugs are safe for patients with cardiovascular risk factors. However, long-term studies are needed to prove cardiovascular safety. The risk of developing medication overuse headache may differ between triptans, ditans and gepants, but further studies are needed to confirm this difference. Head-to-head randomized controlled trials of acute therapies and combinations of therapies are needed to determine their place in migraine treatment among established therapies.

Objective(s): The oral contraceptive pill (OCP) is the most used contraceptive worldwide; nevertheless, discontinuation rates are relatively high. While advantages of the OCP, like pregnancy prevention and planned parenthood, result in autonomy and independence, side effects and other aspects play a role in the decision to (dis)continue usage. Informed and deliberate decision-making is of importance to prevent adverse effects in health and quality of life. Therefore, the present study aimed to explore how women in the Netherlands decide to (dis)continue the OCP. Study design: This paper reports a qualitative study using four focus groups, conducted online or face-to-face, with 20 women of different educational background aged between 18 and 23. The topic guide was based on relevant theory and literature, and focused on personal beliefs, experiences and social interactions about the OCP. The study is reported according to SRQR guidelines. Results: The main themes that were found the influence decision-making were effects, side effects, towards alternatives, interpersonal communication with peers, interpersonal communication with the general practitioner, and online information seeking. Feeling responsible emerged as a relevant additional theme, embedded in the decision-making process, and influencing other themes. Some educational differences emerged. Conclusion(s): The decision to start the OCP is a highly normalized process in the Netherlands. However, women who feel a strong sense of responsibility for pregnancy prevention may be less open to considering alternative contraception methods. Results imply that women can be better supported in the decision-making process by providing balanced information on effects and side effects of a wide range of contraceptives, as well as restoring the balance in both sexual partner's responsibility for contraception. Implications for practice and suggestions for further research on the concept of responsibility, its influence, a

Millions of women worldwide use hormonal contraceptives as an effective form of contraception. However, the focus on their side effects to date has mainly been on the physical aspects, although the most common reason for discontinuation is depression. The main objective of our research is to assess the impact hormonal contraceptives have on mood in women of childbearing age. Surprisingly, there are few studies investigating depression related to hormonal contraceptive use. More research is needed to better inform women and physicians about contraceptive-related depression, as well as clinical guidelines on the different types of oral contraceptives and their possible depressogenic properties. A nationally representative sample of women aged 12 years and older from the 2018 National Health and Nutrition Survey (ENSANUT) was used. We used multicollinearity tests to rule out possible statistical modeling problems and a binary logistic linear regression model where Odds Ratio (OR) with their 95% confidence intervals (95% CI) were estimated for each of the independent variables. In addition, we used specificity tests to test the fit between our dependent and independent variables. That is, our results reveal that the use of hormonal contraceptives increased 3.12-fold (OR=3.12; CI=3.046-3.321) the likelihood of chronic mental illnesses such as depression. This result is statistically significant (p<0.05). It was also demonstrated that women in rural areas with lower income and low schooling are more susceptible to mental disorders compared to the rest of the population. We also showed that variables such as age, a greater number of children, obesity, low schooling, unemployment, being a migrant and greater urban density have a positive influence on the probability of suffering from chronic mental disorders. The results of this study showed that, although poor mental health is correlated with the type of family planning, fear of depression should not be an obstacle to c

Background: Innovations in imaging and molecular characterisation and the evolution of new therapies have improved outcomes in advanced prostate cancer. Nonetheless, we continue to lack high-level evidence on a variety of clinical topics that greatly impact daily practice. To supplement evidence-based guidelines, the 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) surveyed experts about key dilemmas in clinical management. Objective: To present consensus voting results for select questions from APCCC 2022. Design, setting, and participants: Before the conference, a panel of 117 international prostate cancer experts used a modified Delphi process to develop 198 multiple-choice consensus questions on (1) intermediate- and high-risk and locally advanced prostate cancer, (2) biochemical recurrence after local treatment, (3) side effects from hormonal therapies, (4) metastatic hormone-sensitive prostate cancer, (5) nonmetastatic castration-resistant prostate cancer, (6) metastatic castration-resistant prostate cancer, and (7) oligometastatic and oligoprogressive prostate cancer. Before the conference, these questions were administered via a web-based survey to the 105 physician panel members (“panellists”) who directly engage in prostate cancer treatment decision-making. Herein, we present results for the 82 questions on topics 1–3. Outcome measurements and statistical analysis: Consensus was defined as ≥75% agreement, with strong consensus defined as ≥90% agreement. Results and limitations: The voting results reveal varying degrees of consensus, as is discussed in this article and shown in the detailed results in the Supplementary material. The findings reflect the opinions of an international panel of experts and did not incorporate a formal literature review and meta-analysis. Conclusions: These voting results by a panel of international experts in advanced prostate cancer can help physicians and patients navigate controversial areas of clinical man

Background Use of exogenous female sex hormones is associated with the development of asthma, but the question of whether the effect is protective or harmful remains unresolved. Objective To investigate whether initiation of hormonal contraceptive (HC) treatment was associated with development of asthma. Methods We performed a register-based, exposure-matched cohort study including women who initiated HC treatment of any kind between 10 and 40 years of age and compared the incidence of asthma with women who did not initiate HCs. Asthma was defined as 2 redeemed prescriptions of inhaled corticosteroids within 2 years. Data were analyzed using Cox regression models adjusted for income and urbanization. Results We included 184,046 women with a mean age of 15.5 years (SD 1.5 y), in which 30,669 initiated HC treatment and 153,377 did not. We found that initiation of HCs was associated with an increased hazard ratio (HR) of developing new asthma by 1.78 (95% CI 1.58–2.00; P < .001). The cumulative risk of new asthma was 2.7% after 3 years among users of HCs compared with 1.5% in nonusers. In the different subtypes of HCs, second- and third-generation contraceptives carried significant associations (second-generation HR 1.76; 95% CI 1.52–2.03; P < .001; third-generation HR 1.62 95% CI 1.23–2.12; P < .001). The association with increased incidence was seen only in women younger than 18 years. Conclusions In this study, first-time users of HCs had an increased incidence of asthma compared with nonusers. Clinicians prescribing HCs should be aware that airway symptoms may develop., Background: Use of exogenous female sex hormones is associated with the development of asthma, but the question of whether the effect is protective or harmful remains unresolved. Objective: To investigate whether initiation of hormonal contraceptive (HC) treatment was associated with development of asthma. Methods: We performed a register-based, exposure-matched cohort study including women who initiated HC treatment of any kind between 10 and 40 years of age and compared the incidence of asthma with women who did not initiate HCs. Asthma was defined as 2 redeemed prescriptions of inhaled corticosteroids within 2 years. Data were analyzed using Cox regression models adjusted for income and urbanization. Results: We included 184,046 women with a mean age of 15.5 years (SD 1.5 y), in which 30,669 initiated HC treatment and 153,377 did not. We found that initiation of HCs was associated with an increased hazard ratio (HR) of developing new asthma by 1.78 (95% CI 1.58–2.00; P <.001). The cumulative risk of new asthma was 2.7% after 3 years among users of HCs compared with 1.5% in nonusers. In the different subtypes of HCs, second- and third-generation contraceptives carried significant associations (second-generation HR 1.76; 95% CI 1.52–2.03; P <.001; third-generation HR 1.62 95% CI 1.23–2.12; P <.001). The association with increased incidence was seen only in women younger than 18 years. Conclusions: In this study, first-time users of HCs had an increased incidence of asthma compared with nonusers. Clinicians prescribing HCs should be aware that airway symptoms may develop.

Background Recent observational studies suggest that the leukotriene receptor antagonist montelukast may have neuropsychiatric adverse effects; however, results are conflicting. Objective To assess whether montelukast exposure in adults with asthma is associated with onset of neuropsychiatric adverse events using data from the Danish nationwide health registers. Methods Individuals 18 years old or older with either 1 or more prescription redemption of inhaled corticosteroids or with at least 1 hospital contact with asthma as the main diagnosis between January 1, 2011, and December 31, 2018, were included. Montelukast exposure was assessed as a time-dependent variable. The 2 outcomes of interest were use of neuropsychiatric medicine including antidepressants, antipsychotics, anxiolytics, lithium, and medication used for attention-deficit/hyperactivity disorder (outcome 1), and hospital contacts with a neuropsychiatric diagnosis (outcome 2), within 90 days of exposure to montelukast. Results Initiation of montelukast was significantly associated with outcome 1: use of neuropsychiatric medicine (hazard ratio [95% confidence interval]) 1.14 [1.08–1.20]; P < .0001). In the assessment of outcome 2: hospital contacts with a neuropsychiatric diagnosis, a significant risk associated with montelukast initiation was found only in the youngest age groups (hazard ratio [95% confidence interval] 1.28 [1.12–1.47], P < .001 and 1.16 [1.02–1.31]; P < .05, for age group 18–29 y and 30–44 y, respectively). Age-stratified analyses showed that the risk of both outcomes increased with decreasing age, with the highest risk seen in patients aged 18 to 29 years. Conclusions Among younger individuals, montelukast use was significantly associated with an increased risk of neuropsychiatric events such as use of neuropsychiatric medicine and hospital treatment. Clinicians should increase awareness of such adverse effects when pres, Background: Recent observational studies suggest that the leukotriene receptor antagonist montelukast may have neuropsychiatric adverse effects; however, results are conflicting. Objective: To assess whether montelukast exposure in adults with asthma is associated with onset of neuropsychiatric adverse events using data from the Danish nationwide health registers. Methods: Individuals 18 years old or older with either 1 or more prescription redemption of inhaled corticosteroids or with at least 1 hospital contact with asthma as the main diagnosis between January 1, 2011, and December 31, 2018, were included. Montelukast exposure was assessed as a time-dependent variable. The 2 outcomes of interest were use of neuropsychiatric medicine including antidepressants, antipsychotics, anxiolytics, lithium, and medication used for attention-deficit/hyperactivity disorder (outcome 1), and hospital contacts with a neuropsychiatric diagnosis (outcome 2), within 90 days of exposure to montelukast. Results: Initiation of montelukast was significantly associated with outcome 1: use of neuropsychiatric medicine (hazard ratio [95% confidence interval]) 1.14 [1.08–1.20]; P < .0001). In the assessment of outcome 2: hospital contacts with a neuropsychiatric diagnosis, a significant risk associated with montelukast initiation was found only in the youngest age groups (hazard ratio [95% confidence interval] 1.28 [1.12–1.47], P < .001 and 1.16 [1.02–1.31]; P < .05, for age group 18–29 y and 30–44 y, respectively). Age-stratified analyses showed that the risk of both outcomes increased with decreasing age, with the highest risk seen in patients aged 18 to 29 years. Conclusions: Among younger individuals, montelukast use was significantly associated with an increased risk of neuropsychiatric events such as use of neuropsychiatric medicine and hospital treatment. Clinicians should increase awareness of such adverse effects when prescribing montelukast.

Despite the success of mRNA-based vaccines against infectious diseases (including COVID-19), safety concerns have been raised relating to the lipid nanoparticles (LNPs) used to deliver the mRNA cargo. Antibodies against the polyethylene glycol (PEG) coating on these non-viral vectors are present in the general population and can in some instances induce allergic reactions. Furthermore, treatment with PEGylated therapeutics may increase the plasma concentration of such anti-PEG antibodies. The widespread use of PEGylated nanoparticles for mRNA vaccines concerns researchers and clinicians about a potential rise in future cases of allergic reactions against mRNA vaccines and cross-reactions with other PEGylated therapeutics. To determine if vaccination with Comirnaty increased the plasma concentration of antibodies against LNPs, we investigated the blood plasma concentration of anti-LNP antibodies in healthy individuals before and after vaccination with the mRNA-based COVID-19 vaccine Comirnaty (BNT162b2). Blood samples were acquired from 21 healthy adults before vaccination, 3-4 weeks after the first vaccination dose but before the second dose, and 2-6 months after the second (booster) dose. The blood plasma concentration of antibodies recognizing the LNPs was analyzed using a microscopy-based assay capable of measuring antibody-binding to individual authentic LNPs. No significant increase in anti-LNP antibodies was observed after two doses of Comirnaty. The LNPs used for intramuscular delivery of mRNA in the vaccine against COVID-19, Comirnaty, do, therefore, not seem to induce the generation of anti-vector antibodies.

Background: Patients and practitioners often consider the risk of side effects when starting a treatment for psoriasis and often consult reported adverse events (AE) in studies. However, most of these AEs are unrelated to treatment and patients consider what is the risk of an event should you not start a treatment. This is what would be observed in the placebo-arm of clinical trials. Objective: To investigate the proportion of patients experiencing AEs during treatment with placebo in clinical trials. Methods: We conducted a systematic literature search using PubMed, Embase and Web of Science databases for phase 3 randomized clinical trials that registered adverse events of using placebo vs biological agents for psoriasis. The search term was “Psoriasis AND (Phase III OR Phase 3)”. Results: Of 7142 screened articles, 54 were included in the metanalysis. The pooled proportion of placebo-treated patients experiencing any AEs was.52 (95% Cl:.51 to.53) after 12 weeks and.53 (95% Cl:.50 to.55) after 16 weeks. The pooled proportion of patients with any serious AEs was.02 (95% Cl:.01 to.02) and.03 (95% Cl:.02 to.03) after 12 and 16 weeks, respectively. The most common AEs in placebo-treated patients were infections, nasopharyngitis, and headache. Conclusion: About half of the patients with moderate-to-severe psoriasis not starting an active treatment would experience disease events that would be categorized as AEs during a 12-16 weeks period.

Background & Aims: Subcutaneous vedolizumab formulation has been shown to be as effective and safe as the intravenous one in randomized control trials. Real-life data are limited especially for patients receiving long-term intravenous therapy. This study aimed to evaluate the safety and effectiveness of switching from intravenous to subcutaneous vedolizumab in a large cohort of patients with stable clinical remission.Methods: In this prospective cohort study, we enrolled consecutive patients attending our center between September 2021 and April 2022. The baseline demographic characteristics, 12- and 24-weeks follow-up clinical activity, C-reactive protein levels, and adverse events were recorded. The primary endpoint was to assess combined steroid-free clinical remission plus biochemical remission 24-week after the switch.Results: 93 patients (43 Crohn's disease, 50 ulcerative colitis), switched to subcutaneous vedolizumab after a median duration of intravenous treatment of 36 months [IQR 16-52]. At baseline, 80 patients (86%) had a combined remission. At 24-week, 89.2% (n=74) maintained combined steroid-free clinical remission plus biochemical remission. 25 adverse events were reported, mostly SARS-CoV-2 infections and injection site reactions, with a further four recurrence episodes. Twelve patients (12.9%) discontinued subcutaneous administration and restarted intravenous vedolizumab.Conclusions: Switching from intravenous to subcutaneous vedolizumab can be considered effective and safe for maintaining remission in patients with inflammatory bowel disease. In addition, this might reduce healthcare costs. However, large-scale real-life studies with long-term follow-up are necessary.

Vaccination against SARS-CoV-2 is an important and essential strategy to combat the 2019 coronavirus disease (COVID-19) pandemic. Vaccination has shown to be effective in reducing the spread of SARS-CoV-2, reducing the chances of becoming infected and developing severe COVID-19, and reducing hospitalization and mortality rates. However, the vaccinations against SARS-CoV-2 are accompanied by undesirable side effects which may be in part responsible for a reduction in the willingness to become vaccinated. At this moment (June 2022), 24.3% of the US adult population (18+ years old) is not fully vaccinated against SARS-CoV-2, and 49.5% did not receive their follow-up booster vaccination. The most important motives for refusing vaccination are the unknown long-term side effects and the known acute side effects of vaccination. Here, we discuss the importance of recognizing the impact of this reactogenicity on individuals’ willingness to vaccinate and how the development of effective and safe medicines that prevent or mitigate the unwanted side effects of the vaccination may help to increase the willingness to vaccinate.

A considerable number of travelers receive multiple travel vaccinations before going on holiday. Here, we present a case report of a 56-year-old male traveler. On day 1, he received vaccinations against influenza, Tdab (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis), MMR (measles, mumps, and rubella), yellow fever, and cholera. On days 1,3, 5, and 7, he self-administered an oral vaccine against typhoid. Treatment comprised the combination of 220 mg naproxen and 180 mg fexofenadine (SJP-003), to be taken 4h before and 6h after the vaccinations on day 1, and every 12 h thereafter until the end of day 7. Side effects were noted daily, and their severity was scored on a scale ranging from 0 (absent) to 10 (severe). These reports revealed that, except from a slight bruising at the injection site, no side effects were experienced from day 1 to day 4. After the second dose on day 3, treatment was discontinued. Two hours after taking the typhoid vaccine on Day 5, various flu-like symptoms were reported of moderate to high severity, including fever, muscle aches (both with severity score of 8), headache (severity score 7), and nausea (severity score 6). Therefore, at 2 h after typhoid vaccination on day 5, naproxen and fexofenadine were self-administered. At 4 h thereafter, all symptoms were resolved. Treatment was continued at the 12 h schedule. On day 6 and 7, no side effects were reported. Taken together, this case study suggests that the combination of naproxen and fexofenadine was effective in preventing or reducing vaccination side effects. Therefore, more research is warranted to further evaluate the efficacy of SJP-003.

Neospora caninum is an apicomplexan parasite closely related to Toxoplasma gondii, and causes abortions, stillbirths and/or fetal malformations in livestock. Target-based drug development has led to the synthesis of calcium-dependent protein kinase 1 inhibitors, collectively named bumped kinase inhibitors (BKIs). Previous studies have shown that several BKIs have excellent efficacy against neosporosis in vitro and in vivo. However, several members of this class of compounds impair fertility in pregnant mouse models and cause embryonic malformation in a zebrafish (Danio rerio) model. Similar to the first-generation antiprotozoal drug quinine, some BKIs have a quinoline core structure. To identify common targets in both organisms, we performed differential affinity chromatography with cell-free extracts from N. caninum tachyzoites and D. rerio embryos using the 5-aminopyrazole-4-carboxamide (AC) compound BKI-1748 and quinine columns coupled to epoxy-activated sepharose followed by mass spectrometry. BKI-binding proteins of interest were identified in eluates from columns coupled to BKI-1748, or in eluates from BKI-1748 as well as quinine columns. In N. caninum, 12 proteins were bound specifically to BKI-1748 alone, and 105 proteins, including NcCDPK1, were bound to both BKI-1748 and quinine. For D. rerio, the corresponding numbers were 13 and 98 binding proteins, respectively. In both organisms, a majority of BKI-1748 binding proteins was involved in RNA binding and modification, in particular, splicing. Moreover, both datasets contained proteins involved in DNA binding or modification and key steps of intermediate metabolism. These results suggest that BKI-1748 interacts with not only specific targets in apicomplexans, such as CDPK1, but also with targets in other eukaryotes, which are involved in common, essential pathways., Swiss National Science Foundation, National Institutes of Health NIH, US USDA/NIFA, Depto. de Sanidad Animal, Fac. de Veterinaria, TRUE, pub

Leucinostatins are antimicrobial peptides with a broad range of activities against infectious agents as well as mammalian cells. The leucinostatin-derivative peptide ZHAWOC_6027 (peptide 6027) was tested in vitro and in vivo for activity against the intracellular apicomplexan parasite Toxoplasma gondii. While highly efficacious in vitro (EC50 = 2 nM), subcutaneous application of peptide 6027 (3 mg/kg/day for 5 days) in mice experimentally infected with T. gondii oocysts exacerbated the infection, caused mild clinical signs and elevated cerebral parasite load. Peptide 6027 also impaired the proliferation and viability of mouse splenocytes, most notably LPS-stimulated B cells, in vitro. To identify common potential targets in Toxoplasma and murine splenocytes, we performed differential affinity chromatography (DAC) with cell-free extracts from T. gondii tachyzoites and mouse spleens using peptide 6027 or an ineffective analogue (peptide 21,358) coupled to N-hydroxy-succinimide sepharose, followed by mass spectrometry. Proteins specifically binding to peptide 6027 were identified in eluates from the peptide 6027 column but not in peptide 21,358 nor the mock column eluates. In T. gondii eluates, 269 proteins binding specifically to peptide 6027 were identified, while in eluates from mouse spleen extracts 645 proteins specifically binding to this peptide were detected. Both datasets contained proteins involved in mitochondrial energy metabolism and in protein processing and secretion. These results suggest that peptide 6027 interacts with common targets in eukaryotes involved in essential pathways. Since this methodology can be applied to various compounds as well as target cell lines or organs, DAC combined with mass spectrometry and proteomic analysis should be considered a smart and 3R-relevant way to identify drug targets in pathogens and hosts, thereby eliminating compounds with potential side effects before performing tedious and costly safety and efficacy assessme, Swiss National Science Foundation, Depto. de Sanidad Animal, Fac. de Veterinaria, TRUE, pub

Purpose Adjuvant radiotherapy (RT) for breast cancer is associated with an increased risk of ischemic heart disease. We examined the risk of coronary artery stenosis in a large cohort of women with breast cancer receiving adjuvant RT. Methods A cohort of women diagnosed with breast cancer between 1992 and 2012 in three Swedish health care regions (n = 57,066) were linked to the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) to identify women receiving RT who subsequently underwent a percutaneous coronary intervention (PCI) due to coronary stenosis. Cox regression analyses were performed to examine risk of a coronary intervention and competing risk analyses were performed to calculate cumulative incidence. Results A total of 649 women with left-sided breast cancer and 494 women with right-sided breast cancer underwent a PCI. Women who received left-sided RT had a significantly higher risk of a PCI in the left anterior descending artery (LAD) compared to women who received right-sided RT, hazard ratio (HR) 1.44 (95% confidence interval [CI] 1.21-1.77, p < 0.001). For the proximal, mid, and distal LAD, the HRs were 1.60 (95% CI 1.22-2.10), 1.38 (95% CI 1.07-1.78), and 2.43 (95% CI 1.33-4.41), respectively. The cumulative incidence of coronary events at 25 years from breast cancer diagnosis were 7.0% in women receiving left-sided RT and 4.4% in women receiving right-sided RT. Conclusion Implementing and further developing techniques that lower cardiac doses is important in order to reduce the risk of long-term side effects of adjuvant RT for breast cancer.

Background: Group analysis of patients with deep brain stimulation (DBS) has the potential to help understand and optimize the treatment of patients with movement disorders. Probabilistic stimulation maps (PSM) are commonly used to analyze the correlation between tissue stimulation and symptomatic effect but are applied with different methodological variations. Objective: To compute a group-specific MRI template and PSMs for investigating the impact of PSM model parameters. Methods: Improvement and occurrence of dizziness in 68 essential tremor patients implanted in caudal zona incerta were analyzed. The input data includes the best parameters for each electrode contact (screening), and the clinically used settings. Patient-specific electric field simulations (n = 488) were computed for all DBS settings. The electric fields were transformed to a group-specific MRI template for analysis and visualization. The different comparisons were based on PSMs representing occurrence (N-map), mean improvement (M-map), weighted mean improvement (wM-map), and voxel-wise t-statistics (p-map). These maps were used to investigate the impact from input data (clinical/screening settings), clustering methods, sampling resolution, and weighting function. Results: Screening or clinical settings showed the largest impacts on the PSMs. The average differences of wM-maps were 12.4 and 18.2% points for the left and right sides respectively. Extracting clusters based on wM-map or p-map showed notable variation in volumes, while positioning was similar. The impact on the PSMs was small from weighting functions, except for a clear shift in the positioning of the wM-map clusters. Conclusion: The distribution of the input data and the clustering method are most important to consider when creating PSMs for studying the relationship between anatomy and DBS outcome.

Bakgrund I majoriteten av länderna världen över klassas livmoderhalscancer som den näst vanligaste eller den vanligaste cancerdiagnosen hos kvinnor. Sjukdomen som till största del orsakas av ihållande infektioner med humant papillomvirus (HPV) kan bilda cellförändringar som senare utvecklar cancertumörer i livmoderhalsen. Aggressiva behandlingsformer i olika kombinationer sätts in och ger vanligen en rad olika biverkningar som påverkar kvinnorna på olika sätt. Ett sjukdomslidande är ett lidande som orsakas av sjukdomen i sig samt dess behandlingar. Kvinnor som får livmoderhalscancer har därav en ökad tendens till att uppleva ett lidande. Syfte Syftet med studien var att belysa kvinnors erfarenheter och upplevelser av att leva med livmoderhalscancer. Metod En icke-systematisk litteraturöversikt tillämpades och författarna baserade resultatet på 15 vetenskapliga artiklar med kvantitativ samt kvalitativ design. Via databaserna Public Medline (PubMed) samt Cumulative Index to Nursing & Allied Health literature (CINAHL) inhämtades artiklarna med hjälp av olika sökkombinationer. Artiklarna som inkluderades i studien kvalitetsgranskades utifrån bedömningsunderlaget framtaget av Sophiahemmet högskola. Därefter genomfördes en integrerad dataanalys där artiklarna till resultatdelen sorterades in i kategorier och underkategorier, genom detta utformades fyra huvudrubriker med tillhörande underrubriker. Resultat I litteraturöversiktens resultat beskrivs hur kvinnor upplever livmoderhalscancer. I resultatet framkommer det att beskedet om diagnosen, genomförandet av behandling samt dess biverkningar påverkat majoriteten av kvinnornas fysiska, psykiska och sexuella förmåga. I resultatet framkommer det även att majoriteten av kvinnorna som lever med sjukdomen upplever en förändrad vardag med anledning av detta. Slutsats Litteraturöversiktens resultat visar sammanfattningsvis att upplevelsen av livmoderhalscancer är varierande hos kvin, Background In the majority of countries around the world, cervical cancer is classified as the second most common or the most common cancer diagnosis in women. The disease, which is largely caused by persistent infections with human papillomavirus (HPV), can form cell changes that later develop cancerous tumors in the cervix. Aggressive forms of treatment in different combinations are used and usually cause a number of different side effects that affect women in different ways. The suffering of illness is a suffering caused by the disease itself and its treatments. Women who get cervical cancer therefore have an increased tendency to experience suffering. Aim The purpose of this study was to illustrate women's experiences of living with cervical cancer. Method A non-systematic literature overview was applied and the authors based their results from 15 scientific articles with quantitative and qualitative design. The articles are collected from the databases Public Medline (PubMed) and Cumulative Index to Nursing & Allies Health Literature (CINAHL), using different search combinations. The articles included in the study has been quality audited based on the assessment data produced by Sophiahemmet Högskola. Thereafter, an integrated data analysis was carried out where the articles were sorted into categories, and under categories, through this, four main headings with associated subheadings were designed. Results In the result of the literature overview, it is described how women experience cervical cancer. The results show that the information about the diagnosis, the implementation of treatment and its side effects affected the majority of the women's physical, mental and sexual abilities. The results also show that the majority of women living with the disease experience a changed everyday life due to this. Conclusions In summary, the result of the literature overview show that the experience of cervical cancer varies in women, mainly due to the choice of

OBJECTIVE: To ensure the safety and quality of vaccines, especially the newest RNA-vaccines against COVID-19, is one of the World Health Organization's current highest priorities. DESIGN: Case description. STUDY SAMPLE: We report three cases of sudden unilateral tinnitus following BNT162b2 mRNA-vaccine injection, which rapidly resolved in 2 out of 3 cases. RESULTS: The mechanism responsible for its development remains unclear. A hypersensitivity reaction with an abnormal autoimmune response or a vasculitic event may be implicated. CONCLUSIONS: Large-scale and well-designed studies are needed to improve surveillance of the COVID-19 vaccine and better define possible adverse reactions involving the cochleo-vestibular system and/or immunisation anxiety-related reactions.

The invasive apple snail (Pomacea maculata) appeared in 2010 in the Ebro Delta Natural Park, an important area for rice production and waterbird conservation in the eastern Mediterranean. To control crop damage, farmers stopped flooding their rice fields in winter, an agri-environmental scheme (AES) applied for more than 20 years in some European and American regions to favor flora and fauna from wetlands, including wintering waterbirds. Thus, apple snail control is controversial because of its potential side effects on international waterbird conservation efforts. Despite the fact that 10 years have passed since the first flooding limitations, and the alarms raised by the managers of the Natural Park, the side effects of apple snail management on waterbird conservation have not been evaluated. Here we fill this gap by analyzing a 35-year time series to assess whether abundance trends of 27 waterbird species, from five functional groups, decreased in the Ebro Delta after stopping winter flooding. We considered the effects of confounding local factors by also assessing trend changes in l’Albufera, a similar nearby not invaded wetland where flooding has not been interrupted. In addition, as a control of the positive effect of winter flooding, we also assessed whether abundance trends increased in both wetlands after applying this AES winter flooding. Our results showed complex and decoupled trend changes across species and geographical areas, without statistical evidences, in general or for any particular functional group, on the positive effect of winter flooding in both wetlands neither on the negative effect of its cessation in Ebro Delta. These results suggest the safety of this apple snail control in terms of waterbird abundance at a landscape scale. In addition, these results question, at least in two important wintering areas in Europe, the attractor role associated with the flooding agri-environmental scheme applied for decades

The aim of this study was to investigate the pre-impressions of the third Coronavirus disease 2019 (COVID-19) vaccination among Japanese medical staff using quantitative analysis. Among 413 medical staff, 260 (60 men and 200 women) aged 40.4 ± 12.3 years were enrolled in this cross-sectional study. Pre-impressions of the third COVID-19 vaccination were analyzed using the text-mining analysis software, KH coder. Among 260 subjects, 242 (93.1%) agreed to the third vaccination, with the rate being lower among subjects in their 30s (87.3%) than those in the other age groups. The word “side effects” was characteristic of subjects in their 20s and nurses, and “pregnancy” of those in their 30s and administrative staff. Pre-impressions of the third COVID-19 vaccination varied among age groups and different professions. The results obtained provide useful information for promoting the third COVID-19 vaccination to Japanese adults.

Background: Individuals with underlying chronic illnesses have demonstrated considerable hesitancy towards COVID-19 vaccines. These concerns are primarily attributed to their concerns over the safety profile. Real-world data on the safety profile among COVID-19 vaccinees with comorbid conditions are scarce. This study aimed to ascertain the side-effects profile after two doses of COVID-19 vaccines among chronic-disease patients. Methodology: A cross-sectional questionnaire-based study was conducted among faculty members with comorbid conditions at a public educational institute in Saudi Arabia. A 20-item questionnaire recorded the demographics and side effects after the two doses of COVID-19 vaccines. The frequency of side effects was recorded following each dose of vaccine, and the association of the side-effects score with the demographics was ascertained through appropriate statistics. Results: A total of 204 patients with at least one comorbid condition were included in this study. A total of 24 side effects were reported after the first dose and 22 after second dose of the COVID-19 vaccine. The incidence of at least one side effect was 88.7% and 95.1% after the first and second doses of the vaccine, respectively. The frequent side effects after the first dose were pain at the injection site (63.2%), fatigue (58.8%), fever (47.5%), muscle and joint pain (38.7%), and headache (36.3%). However, pain at the injection site (71.1%), muscle and joint pain (62.7%), headache (49.5%), fever (45.6%), and stress (33.3%) were frequent after the second dose. The average side-effects score was 4.41 +/- 4.18 (median: 3, IQR: 1, 6) and 4.79 +/- 3.54 (median 4, IQR: 2, 6) after the first and second dose, respectively. Female gender, diabetes mellitus, hypertension, hyperlipidemia, comorbidity > 2, family history of COVID-19, and the AstraZeneca vaccine were significantly associated with higher side-effect scores. Only 35.8% of study participants were satisfied with the safety