| 1. |
- Rask, Olof, et al.
(författare)
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Oestrogen treatment of constitutional tall stature in girls: is there a risk of thrombosis or bleeding?
- 2008
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Ingår i: Acta Pædiatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 97:3, s. 342-347
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To evaluate haemostatic effects and clinical outcome of oestrogen treatment of constitutionally tall stature in girls. Methods: We conducted a single-centre cohort study, 63 girls referred over a period of 15 years were investigated. The girls were given oestrogen treatment for constitutional tall stature at a median initial dose of 300 ug ethinyl estradiol/day and were consecutively examined for changes in coagulation. Medical records were retrospectively reviewed, additional data were collected at follow-up by blood sampling and interviews. Results: After 1 year of treatment, levels of antithrombin and von Willebrand factor (VWF) were significantly decreased (p < 0.001 and p = 0.015, respectively), whereas there was no significant change in levels of plasminogen inhibitor type 1. No venous thromboembolism (VTE) or major side effects were observed. Genetic risk factors for thrombosis were present, as was expected. The mean height reduction was 5.5 cm. The height-reducing effect was inversely correlated with chronological age (r =-0.44, p < 0.01) and bone age (r =-0.61, p < 0.01). Conclusions: Changes in coagulation parameters occurred both towards pro- and anticoagulation. Treatment with high-dose ethinyl estradiol can successfully limit final height, and it is most effective when started at a younger bone age.
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| 2. |
- Welin, Karl-Olof, et al.
(författare)
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Epilepsy in tuberous sclerosis patients in Sweden – Healthcare utilization, treatment, morbidity, and mortality using national register data
- 2017
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Ingår i: Seizure. - : Elsevier BV. - 1059-1311. ; 53, s. 4-9
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Tidskriftsartikel (refereegranskat)abstract
- Purpose This study is designed to estimate the prevalence of epilepsy associated with TSC in Sweden and to describe treatment, morbidity, and mortality of TSC patients with epilepsy. Methods Register data for 2004–2014 was obtained from the National Board of Health and Welfare in Sweden. Patients with TSC were identified using ICD-10 codes. Epilepsy was identified using ICD-10 codes, interventions aimed to treat epilepsy, or prescriptions for antiepileptic drugs. Results The prevalence of TSC was 5.38 per 100 000 individuals. We identified 551 unique patients with TSC, of which 386 (70.1%) had epilepsy. The mean study period was 8.82 years. Antiepileptic drugs were dispensed to 97.9% of patients with epilepsy. The most prescribed antiepileptic drug was sodium valproate. Ketogenic diet was used in 6 (1.6%) patients, vagus nerve stimulation in 23 (6.0%) patients, and epilepsy surgery was performed in 25 (6.5%) patients. The mean number of outpatient visits per year was 4.70 (SD 4.17) and the mean number of inpatient days per year was 3.25 (SD 5.61). The mean number of outpatient visits per year with an ICD-10 code for epilepsy was 1.65 (SD 1.95) and the corresponding number of inpatient days was 2.06 (SD 4.50). A total of 30 patients with TSC and epilepsy died during the study period. Conclusions The prevalence of epilepsy in this study was in the lower range of previously reported numbers, suggesting that epilepsy may be overestimated in non-population based studies. A substantial part of the healthcare utilization was directly related to epilepsy.
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| 3. |
- Arnison, Tor, Filosofie doktor, 1984-, et al.
(författare)
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Safety of and response to electroconvulsive therapy during pregnancy : Results from population‐based nationwide registries
- 2023
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Ingår i: Acta Psychiatrica Scandinavica. - : John Wiley & Sons. - 0001-690X .- 1600-0447.
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Psychiatric disorders are common during pregnancy, affecting up to 16% of pregnant women. Severe depression and anxiety have significant negative effects on the health of both the mother and the developing fetus. Electroconvulsive therapy (ECT) is considered a treatment option for pregnant women with severe psychiatric disorders when other treatments have been ineffective or pose risks to the fetus. Knowledge of the safety and efficacy of ECT during pregnancy, however, remains limited.Methods: Data were obtained from nationwide registries of pregnant women in Sweden who received ECT for a severe psychiatric disorder from January 2008 to December 2021. ECT-related outcomes in pregnant women were compared by propensity score matching with a group of non-pregnant women who also received ECT. Pregnancy-related outcomes were compared with two additional control groups: one consisting of the same group of women who did not receive ECT during another pregnancy and the other composed of pregnant women admitted to inpatient psychiatric care but who did not receive ECT, matched based on propensity score.Results: Ninety-five pregnant women received ECT during the study period, accounting for 97 pregnancies. The response rate to ECT in pregnant women (n = 54) was similar to the matched control group of non-pregnant women (74% vs. 65%; OR 1.61; 95% CI 0.79-3.27). Rates of adverse events related to ECT were similar to those in the control group. There were no pre-term births or severe adverse outcomes related to the pregnancy, that were close in time to ECT. Therefore, no adverse outcomes related to pregnancy and childbirth could be directly attributed to ECT. The likelihood of premature birth and a 5-min Apgar score <7 in the newborn were both significantly higher in the ECT group, compared with the matched non-ECT group (OR 2.33, 95% CI 1.15-4.73, p = 0.008, and OR 3.68, 95% CI 1.58-8.55, p < 0.001, respectively). By contrast, no significant differences were observed when women in the pregnant ECT group were compared with the same group lacking ECT during another pregnancy.Conclusions: ECT was associated with a positive treatment response in pregnant women with severe psychiatric disorders. The response rate to ECT was similar in pregnant and non-pregnant women. Nevertheless, the risks of premature birth and of a slightly poorer condition in newborns were higher in women who did than did not receive ECT, emphasizing the need for increased attention to severe psychiatric disorders during pregnancy.
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| 4. |
- Bäckström, Beata, et al.
(författare)
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Adolescent and Family-Focused Cognitive-Behavioral Therapy for Pediatric Bipolar Disorders : An Open Trial and Individual Trajectories Study in Routine Psychiatric Care
- 2024
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Ingår i: Child Psychiatry and Human Development. - : Springer Science and Business Media LLC. - 0009-398X .- 1573-3327.
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Tidskriftsartikel (refereegranskat)abstract
- Psychosocial treatments improve outcome in Pediatric bipolar disorder (PBD), but few are developed specifically for adolescents and none has been evaluated in Europe. This study evaluates family-focused cognitive-behavioral therapy for adolescents (ages 13-18) with PBD in routine psychiatric care in Sweden, adapted for teenagers in a European setting from the Child and Family-Focused Cognitive Behavioral Therapy for PBD (ages 8-12) developed in the US. In a repeated-measure open trial, psychosocial functioning, depression, skills and knowledge about PBD, and family climate were assessed at pre-treatment, post-treatment, and after 6 months. Assessments were made by adolescents (n = 45), parents (n = 61) and clinicians. Both group statistics and individual trajectories are reported. Psychosocial function, as rated by parents and clinicians, improved at post-treatment, and parents reported less mania and improved family climate at post-treatment. Both parents and adolescents reported improved skills and knowledge. Most results after treatment showed medium effect sizes. Significant improvements were seen in most individual trajectories, however no change and even deterioration was observed in some. The present trial shows that AFF-CBT is well accepted and associated with improved psychosocial function in adolescents and improved skills and knowledge about PBD in adolescents and their parents. Regarding mood symptoms and family climate the results showed more individual variability, indicating that adjustments in delivery of the treatment according to the unique patient could be of importance. AFF-CBT seems to be a valuable addition to pharmacological treatments in PBD.
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| 5. |
- de Vries, Petrus J, et al.
(författare)
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Natural clusters of tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND) : new findings from the TOSCA TAND research project
- 2020
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Ingår i: Journal of Neurodevelopmental Disorders. - : Springer Science and Business Media LLC. - 1866-1955 .- 1866-1947. ; 12:1, s. 24-24
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND) have unique, individual patterns that pose significant challenges for diagnosis, psycho-education, and intervention planning. A recent study suggested that it may be feasible to use TAND Checklist data and data-driven methods to generate natural TAND clusters. However, the study had a small sample size and data from only two countries. Here, we investigated the replicability of identifying natural TAND clusters from a larger and more diverse sample from the TOSCA study.METHODS: As part of the TOSCA international TSC registry study, this embedded research project collected TAND Checklist data from individuals with TSC. Correlation coefficients were calculated for TAND variables to generate a correlation matrix. Hierarchical cluster and factor analysis methods were used for data reduction and identification of natural TAND clusters.RESULTS: A total of 85 individuals with TSC (female:male, 40:45) from 7 countries were enrolled. Cluster analysis grouped the TAND variables into 6 clusters: a scholastic cluster (reading, writing, spelling, mathematics, visuo-spatial difficulties, disorientation), a hyperactive/impulsive cluster (hyperactivity, impulsivity, self-injurious behavior), a mood/anxiety cluster (anxiety, depressed mood, sleep difficulties, shyness), a neuropsychological cluster (attention/concentration difficulties, memory, attention, dual/multi-tasking, executive skills deficits), a dysregulated behavior cluster (mood swings, aggressive outbursts, temper tantrums), and an autism spectrum disorder (ASD)-like cluster (delayed language, poor eye contact, repetitive behaviors, unusual use of language, inflexibility, difficulties associated with eating). The natural clusters mapped reasonably well onto the six-factor solution generated. Comparison between cluster and factor solutions from this study and the earlier feasibility study showed significant similarity, particularly in cluster solutions.CONCLUSIONS: Results from this TOSCA research project in an independent international data set showed that the combination of cluster analysis and factor analysis may be able to identify clinically meaningful natural TAND clusters. Findings were remarkably similar to those identified in the earlier feasibility study, supporting the potential robustness of these natural TAND clusters. Further steps should include examination of larger samples, investigation of internal consistency, and evaluation of the robustness of the proposed natural clusters.
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| 6. |
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| 7. |
- Eberhard, Sophia, et al.
(författare)
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Risky Alcohol Use and Comorbidity in a Swedish Adolescent Emergency Psychiatric Inpatient Population.
- 2021
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Ingår i: Journal of addiction. - : Hindawi Limited. - 2090-7834 .- 2090-7850. ; 2021
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Tidskriftsartikel (refereegranskat)abstract
- Introduction. Underage drinking is associated with poor mental health. Early detection for risky alcohol use is recommended,although less implemented in adolescent care. +e objective of this study was to investigate the prevalence of risky alcohol use andpsychiatric comorbidity. Methods. Over a nine-month period, 145 eligible adolescents admitted to the child and adolescentemergency unit in Malmo, Sweden, were offered computerized screening with Alcohol Use Disorder Identification Test- ¨Consumption (AUDIT-C) and Drug Use Disorders Identification Test (DUDIT). Results. Ninety-six patients (73 girls and 23boys) agreed to participate. +e most common diagnoses were affective disorder (41%) and anxiety disorder (27%). Risky alcoholuse was found among 33% of the girls and 22% of the boys (p � 0.45) and did not differ between diagnostic categories. +ere was apositive correlation between AUDIT-C and DUDIT scores (p � 0.019). Among adolescents with risky alcohol use, 33% of the girlsand 60% of the boys also had a risky drug use. Conversely, 47% of the girls and 60% of the boys with risky drug use also had a riskyalcohol use. Conclusion. In view of the poor prognosis of risky
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| 8. |
- Edvardsson Rasmussen, Jesper, 1984-
(författare)
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Inner ear proteomics and barriers : Clinical and experimental findings
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hearing is important in many aspects of life, including communication, assessing one’s surroundings, entertainment and social interaction. Hearing loss is common and according to the Global Burden of Disease Study, 5% of the global population require hearing rehabilitation (1). Pharmacological treatment options are limited, so understanding cellular mechanisms in the damaged inner ear is crucial for developing novel therapies.In this thesis, the human inner ear proteome in patients with sporadic vestibular schwannoma (VS) and its association with hearing loss were investigated. Ototoxic effects induced by furosemide were also examined, focusing on inner ear barrier function, furosemide sensitive Na-K-Cl co-transporter 1 (NKCC1), Fetuin-A, linked to tumour-associated hearing loss, and Pigment epithelium-derived factor (PEDF), potentially important for blood-endolymph barrier integrity.Translabyrinthine surgery on 35 patients, 32 with VS and three with meningioma, provided samples from perilymph, endolymph, endolymphatic sac tissue, VS biopsies and cerebrospinal fluid (CSF) for proteome analysis. Effects of furosemide on the inner ear barriers were studied in mice using 9.4Tesla MRI, and in guinea pigs using immunohistochemistry and mRNA in situ hybridisation focusing on NKCC1, Fetuin-A, and PEDF.Proteomic analysis revealed consistent sets of proteins in perilymph (91/315) and endolymph (545/1211). The proteomes of perilymph and CSF exhibited specific differences, with proteins unique to each fluid, thereby emphasizing the distinct origin of perilymph separate from CSF. Fetuin-A was inversely related to tumour-associated hearing loss, while patients with severe to profound hearing loss exhibited upregulation of complement factor H-related protein 2 (CFHR2).Furosemide compromised the blood-endolymph barrier, allowing gadolinium contrast into scala media. It affected NKCC1 of type II fibrocytes coinciding with the onset of hearing loss following high-dose furosemide, suggesting early disruption in potassium ion recirculation. Fetuin-A and PEDF were identified in the cochlea at protein and mRNA level. Their staining intensity increased in various cochlear subsites 120 minutes after furosemide administration, indicating their involvement in the cochlear response to the effects of furosemide.In summary, this thesis uncovered significant inter-individual variability in both the perilymph and endolymph proteome, alongside a consistent subset of proteins. Further, associations between hearing loss and proteome changes suggest inflammation as a potential mechanism for hearing degradation caused by vestibular schwannomas. Experimentally, impact of furosemide on blood-inner ear barriers were visualised in vivo and type II fibrocytes were identified as potential initial targets for NKCC1 blockade. Fetuin-A and PEDF were confirmed in several cell types in the cochlea and may increase in response to very high furosemide doses.
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| 9. |
- Edvardsson Rasmussen, Jesper, et al.
(författare)
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The Acute Effects of Furosemide on Na-K-Cl Cotransporter-1, Fetuin-A and Pigment Epithelium-Derived Factor in the Guinea Pig Cochlea
- 2022
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Ingår i: Frontiers in Molecular Neuroscience. - : Frontiers Media S.A.. - 1662-5099. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Furosemide is a loop diuretic used to treat edema; however, it also targets the Na-K-Cl cotransporter-1 (NKCC1) in the inner ear. In very high doses, furosemide abolishes the endocochlear potential (EP). The aim of the study was to gain a deeper understanding of the temporal course of the acute effects of furosemide in the inner ear, including the protein localization of Fetuin-A and PEDF in guinea pig cochleae. Material and Method: Adult guinea pigs were given an intravenous injection of furosemide in a dose of 100 mg per kg of body weight. The cochleae were studied using immunohistochemistry in controls and at four intervals: 3 min, 30 min, 60 min and 120 min. Also, cochleae of untreated guinea pigs were tested for Fetuin-A and PEDF mRNA using RNAscope (R) technology. Results: At 3 min, NKCC1 staining was abolished in the type II fibrocytes in the spiral ligament, followed by a recovery period of up to 120 min. In the stria vascularis, the lowest staining intensity of NKCC1 presented after 30 min. The spiral ganglion showed a stable staining intensity for the full 120 min. Fetuin-A protein and mRNA were detected in the spiral ganglion type I neurons, inner and outer hair cells, pillar cells, Deiters cells and the stria vascularis. Furosemide induced an increased staining intensity of Fetuin-A at 120 min. PEDF protein and mRNA were found in the spiral ganglia type I neurons, the stria vascularis, and in type I and type II fibrocytes of the spiral ligament. PEDF protein staining intensity was high in the pillar cells in the organ of Corti. Furosemide induced an increased staining intensity of PEDF in type I neurons and pillar cells after 120 min. Conclusion: The results indicate rapid furosemide-induced changes of NKCC1 in the type II fibrocytes. This could be part of the mechanism that causes reduction of the EP within minutes after high dose furosemide injection. Fetuin-A and PEDF are present in many cells of the cochlea and probably increase after furosemide exposure, possibly as an otoprotective response.
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| 10. |
- Edvardsson Rasmussen, Jesper, et al.
(författare)
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The proteome of perilymph in patients with vestibular schwannoma : A possibility to identify biomarkers for tumor associated hearing loss?
- 2018
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 13:6
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Tidskriftsartikel (refereegranskat)abstract
- Background Due to the surrounding bone, the human inner ear is relatively inaccessible and difficult to reach for cellular and molecular analyses. However, these types of investigations are needed to better understand the etiology, pathophysiology and progression of several inner ear disorders. Moreover, the fluid from the inner ear cannot be sampled for micro-chemical analyses from healthy individuals in vivo. Therefore, in the present paper, we studied patients with vestibular schwannoma (VS) undergoing trans-labyrinthine surgery (TLS). Our primary aim was to identify perilymph proteins in patients with VS on an individual level. Our second aim was to investigate the proteins identified at a functional level and our final aim was to search for biological markers for tumor-associated hearing loss and tumor diameter. Methods and findings Sixteen patients underwent TLS for sporadic VS. Perilymph was aspirated through the round window before opening the labyrinth. One sample was contaminated and excluded resulting in 15 usable samples. Perilymph samples were analyzed with an online tandem LTQ-Orbitrap mass spectrometer. Data were analyzed with MaxQuant software to identify the total number of proteins and to quantify proteins in individual samples. Protein function was analyzed using the PANTHER Overrepresentation tool. Associations between perilymph protein content, clinical parameters, tumor-associated hearing loss and tumor diameter were assessed using Random Forest and Boruta. In total, 314 proteins were identified; 60 in all 15 patients and 130 proteins only once in 15 patients. Ninety-one proteins were detected in at least 12 out of 15 patients. Random Forest followed by Boruta analysis confirmed that alpha-2-HS-glycoprotein (P02765) was an independent variable for tumor-associated hearing loss. In addition, functional analysis showed that numerous processes were significantly increased in the perilymph. The top three enriched biological processes were: 1) secondary metabolic processes; 2) complement activation and 3) cell recognition. Conclusions The proteome of perilymph in patients with vestibular schwannoma has an inter-individual stable section. However, even in a cohort with homogenous disease, the variation between individuals represented the majority of the detected proteins. Alpha-2-HS-glycoprotein, P02765, was shown to be an independent variable for tumor-associated hearing loss, a finding that needs to be verified in other studies. In pathway analysis perilymph had highly enriched functions, particularly in terms of increased immune and metabolic processes.
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