| 1. |
- Studahl, Marie, 1957, et al.
(författare)
-
Acute viral infections of the central nervous system in immunocompetent adults: diagnosis and management.
- 2013
-
Ingår i: Drugs. - : Springer Science and Business Media LLC. - 0012-6667 .- 1179-1950. ; 73:2, s. 131-58
-
Forskningsöversikt (refereegranskat)abstract
- Patients with viral infections of the central nervous system (CNS) may present with a variety of neurological symptoms, most commonly dominated by either encephalitis or meningitis. The aetiological panorama varies in different parts of the world as well as over time. Thus, virological first-line diagnostics must be adapted to the current epidemiological situation and to the individual patient history, including recent travels. This review focuses on the diagnostics and treatment of viral CNS infections in the immunocompetent host from a Northern European perspective. Effective vaccines are available for viruses such as poliovirus and tick-borne encephalitis virus (TBEV) and for the childhood diseases morbilli (measles), rubella (German measles), parotitis (mumps) and varicella (chickenpox). However, cases do appear due to suboptimal immunization rates. In viral CNS infections, epidemiological surveillance is essential for establishing preventive strategies and for detecting emerging viruses. Knowledge of the possibilities and limitations of diagnostic methods for specific viral CNS infections is vital. A positive cerebral spinal fluid (CSF) polymerase chain reaction (PCR) finding is usually reliable for aetiological diagnosis. The demonstration of intrathecal antibody synthesis is useful for confirming the aetiology in a later stage of disease, hitherto sufficiently evaluated in herpes simplex encephalitis (HSE) and tick-borne encephalitis (TBE). Despite improved virological and differential diagnostic methods, aetiology remains unknown in about half of the cases with suspected viral encephalitis. Antiviral treatment is available chiefly for infections caused by herpesviruses, and acyclovir (aciclovir) is the drug of choice for empirical therapy in suspected viral encephalitis. However, randomized, controlled antiviral trials have only been conducted for HSE, while such studies are lacking in other viral CNS infections. Viral cytolysis and immune-mediated mechanisms may contribute to varying extents to neurological damage. Although the brain damage is believed to depend, to a varying degree, on the intrathecal host immune response, the use of corticosteroids in viral CNS infections is scarcely studied, as is specific treatment for neuroinflammation. Improved antiviral and immunomodulating treatment is desirable. Since neurological sequelae are still abundant, follow-up after severe viral CNS disease must include a neuropsychological assessment and an individually adapted rehabilitation plan.
|
|
| 2. |
- Dunberger, Gail, et al.
(författare)
-
Lower limb lymphedema in gynecological cancer survivors-effect on daily life functioning.
- 2013
-
Ingår i: Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. - : Springer Science and Business Media LLC. - 1433-7339 .- 0941-4355. ; 21:11, s. 3063-70
-
Tidskriftsartikel (refereegranskat)abstract
- Lower limb lymphedema (LLL) is a common condition after pelvic cancer treatment but few studies have evaluated its effect on the quality of life and its consequences on daily life activities among gynecological cancer survivors.
|
|
| 3. |
|
|
| 4. |
- Hugosson, Svante, et al.
(författare)
-
Invasive Haemophilus influenzae Disease : Epidemiology and Clinical Spectrum Before Large-scale H. influenzae Type b Vaccination
- 1995
-
Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 27:1, s. 63-67
-
Tidskriftsartikel (refereegranskat)abstract
- In a prospective study between January 1987 and December 1992, 103 patients with invasive Haemophilus influenzae (Hi) infection were identified in a well-defined population before large-scale Haemophilus influenzae type b (Hib) vaccination was introduced. The incidence (cases/100,000/year) of invasive Hi infection was 5.9 for the whole population, 55 for children 0-4 years old and as high as 2.8 for adults. Hib was the predominant cause of the infection (83 cases) in children but, in adults, 13/39 (30%) cases were caused by non-typable Hi and 6/39 (19%) by Hi serotype f. Three patients (3%) died and 6 (5.8%) suffered a permanent sequel from the infection. All patients with such a sequel had invasive Hib infection. No significant difference between patients 0-6 years old and matched controls regarding the frequency of subnormal serum levels of immunoglobulins was found.
|
|
| 5. |
- Lindquist, Barbro, 1950, et al.
(författare)
-
Quality of life in adults treated in infancy for hydrocephalus.
- 2014
-
Ingår i: Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery. - : Springer Science and Business Media LLC. - 1433-0350. ; 30:8, s. 1413-1418
-
Tidskriftsartikel (refereegranskat)abstract
- The objective was to analyze quality of life in a very long-term follow-up study of now adult individuals, treated for hydrocephalus (without spina bifida) during infancy. METHODS: The entire series was population-based, and the subgroup under study consisted of the 29 individuals without intellectual disability, who consented to participate. About one third had concomitant mild cerebral palsy or epilepsy or both. A Finnish validated questionnaire, the 15D, was used to measure quality of life. RESULTS: There was no significant difference between the study group and the controls with regard to the total quality of life score. Individuals with associated cerebral palsy and/or epilepsy had a lower total score compared with both those without associated impairments and controls. Most participants differed from controls in the dimension of mental/memory function which pertains to executive functions, an ability of considerable importance for daily life skills. CONCLUSION: It is important to follow children with hydrocephalus over time-due to the different etiological panorama, interventions, and associated impairments this group displays. This is the only way to learn more about critical factors that require attention and that predict quality of life in adulthood.
|
|
| 6. |
- Lindquist, Barbro, 1950, et al.
(författare)
-
Very long-term follow-up of cognitive function in adults treated in infancy for hydrocephalus.
- 2011
-
Ingår i: Child'S Nervous System. - : Springer Science and Business Media LLC. - 1433-0350 .- 0256-7040. ; 27:4, s. 597-601
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The aim was to investigate the very long-term cognitive outcome in adults who had been shunt treated for hydrocephalus during their first year of life. METHODS: In a population-based series of 72 children born in 1967-1978 and shunt treated for infantile hydrocephalus, 43 were found to have a normal cognitive function when assessed at 6-17years of age. Twenty-five of them agreed to participate in a follow-up study of cognition at a mean age of 35years (range, 30-41years). The Wechsler Adult Intelligence Scale (WAIS-III) was used. RESULTS: The median full-scale IQ was 101 (range, 83-120), median verbal IQ was 104 (81-115) and performance IQ was 99 (80-127). The corresponding IQs in childhood in the 16 subjects who had been tested previously with the WISC were 101 (84-124), 108 (86-135), and 101 (73-124). Specific cognitive deficits were found for working memory and processing speed. Shunt complications did not affect IQ. CONCLUSION: This very long-term follow-up study of normally gifted children with hydrocephalus revealed that, as adults, they still had preserved cognitive functions despite recurrent shunt dysfunction. The results are encouraging and represent a tribute to neurosurgical intervention. Continued follow-up studies are needed since the etiological panorama and treatment procedures of children with hydrocephalus are changing over time.
|
|
| 7. |
- Lindquist, Ingegerd, 1950, et al.
(författare)
-
Evaluation of process-oriented supervision of student nurses: A Swedish case study
- 2012
-
Ingår i: Nursing and Health Sciences. - : Wiley. - 1441-0745. ; 14:1, s. 2-7
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract The value of supervision that is provided to student nurses during their education is high.The aim of this study was to evaluate the organizational changes in an educational program for Swedish student nurses, focusing on the content and quality of process-oriented supervision. The research question was: Do the organizational changes pertaining to the student nurses’ supervision (its reduced frequency and mandatory nature) influence its content and quality and, if so, in which ways? The data were collected by focus group discussions and were analyzed by a qualitative content analysis. Three themes emerged: difficulties with the new organization, the content and learning outcomes of supervision, and the nurse supervisors’ intentions. Supervision is recommended in order to achieve the goal of nursing education and to ensure that student nurses gain an understanding of their experiences, thus equipping them with the professional skills and competence that are required to meet patients’ needs.
|
|
| 8. |
- Lu, Sai San Moon, et al.
(författare)
-
Antibiotics Use and Subsequent Risk of Colorectal Cancer : A Swedish Nationwide Population-Based Study
- 2022
-
Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 114:1, s. 38-46
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Antibiotics use may increase colorectal cancer (CRC) risk by altering the gut microbiota, with suggestive evidence reported. Our study aims to investigate antibiotics use in relation to subsequent CRC risk.METHODS: This is a nationwide, population-based study with a matched case-control design (first primary CRC cases and 5 matched, cancer-free controls). Complete-population data, extracted from Swedish national registers for the period 2005-2016, were used to calculate odds ratios and 95% confidence intervals.RESULTS: We included 40 545 CRC cases and 202 720 controls. Using the full dataset, we found a positive association between more frequent antibiotics use and CRC, excluding antibiotics prescribed within 2 years of diagnosis attenuated results toward the null. In site-specific analyses, excluding the 2-year washout, the positive association was confined to the proximal colon (adjusted odds ratio for very high use vs no use = 1.17, 95% confidence interval = 1.05 to 1.31). For rectal cancer, an inverse association, which appears to be driven by women, was observed. Quinolones and sulfonamides and/or trimethoprims were positively associated with proximal colon cancer, whereas a more general inverse association, across antibiotics classes, was observed for rectal cancer. We found no association between methenamine hippurate, a urinary tract antiseptic not affecting the gut microbiota, and CRC risk.CONCLUSIONS: This register-based study covering the entire population of Sweden found a robust association between antibiotics use and higher risk of proximal colon cancer and an inverse association with rectal cancer in women. This study strengthens the evidence from previous investigations and adds important insight into site-specific colorectal carcinogenesis.
|
|
| 9. |
- Mullins, Niamh, et al.
(författare)
-
Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
- 2022
-
Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
|
|
| 10. |
- Orikiiriza, Judy, et al.
(författare)
-
Lipid response patterns in acute phase paediatric Plasmodium falciparum malaria
- 2017
-
Ingår i: Metabolomics. - : Springer Science and Business Media LLC. - 1573-3882 .- 1573-3890. ; 13:4
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Several studies have observed serum lipid changes during malaria infection in humans. All of them were focused at analysis of lipoproteins, not specific lipid molecules. The aim of our study was to identify novel patterns of lipid species in malaria infected patients using lipidomics profiling, to enhance diagnosis of malaria and to evaluate biochemical pathways activated during parasite infection.Methods: Using a multivariate characterization approach, 60 samples were representatively selected, 20 from each category (mild, severe and controls) of the 690 study participants between age of 0.5–6 years. Lipids from patient’s plasma were extracted with chloroform/methanol mixture and subjected to lipid profiling with application of the LCMS-QTOF method.Results: We observed a structured plasma lipid response among the malaria-infected patients as compared to healthy controls, demonstrated by higher levels of a majority of plasma lipids with the exception of even-chain length lysophosphatidylcholines and triglycerides with lower mass and higher saturation of the fatty acid chains. An inverse lipid profile relationship was observed when plasma lipids were correlated to parasitaemia.Conclusions: This study demonstrates how mapping the full physiological lipid response in plasma from malaria-infected individuals can be used to understand biochemical processes during infection. It also gives insights to how the levels of these molecules relate to acute immune responses.
|
|
| 11. |
- Persson, Eva-Karin, 1956, et al.
(författare)
-
Very long-term follow-up of adults treated in infancy for hydrocephalus.
- 2011
-
Ingår i: Child's Nervous System. - : Springer Science and Business Media LLC. - 1433-0350 .- 0256-7040. ; 27:9, s. 1477-1481
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The purpose of this study is to perform a population-based, very long-term follow-up of adults who had been shunt treated for hydrocephalus in infancy. METHODS: The 72 children with hydrocephalus born in 1967-1978 in western Sweden, who had participated in a follow-up at school age, were re-examined at 30-43years of age. The 29 with mental retardation were described in terms of developmental level and survival, whereas the remaining 43 were invited to take part in a follow-up and 28 accepted. The assessments included a semi-structured interview pertaining to medical issues, academic achievements and social function. RESULTS: Six children had died, i.e. a mortality rate of 8%. Mental retardation was present in 29 (40%), severe (IQ <50) in 13 and mild (IQ 50-70) in 16. Four of the 28 (14%) had cerebral palsy and 8 (28%) had other motor problems. Five (18%) had epilepsy and nine (32%) had visual impairments. A total of 20 (71%) reported some kind of health problem. Repeated revisions of the shunt had been performed in 23 (82%). Many worried about their shunt and requested a systematic medical follow-up. Nineteen subjects (68%) lived with a partner and 16 (57%) were parents. The majority had completed secondary school and 9 (32%) had completed university studies, while 18 (64%) worked full time, equal to the general population. CONCLUSION: In general, the group of normally gifted individuals with hydrocephalus, who had been shunt treated during infancy, was functioning well as adults and participated in society to the same extent as other people.
|
|
| 12. |
- Reuterswärd, Philippa, et al.
(författare)
-
Levels of human proteins in plasma as indicators for acute severe pediatric malaria
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundExisting low resource diagnostics for malaria infection suffer from sensitivity and specificity issues while lacking sufficient prognostic value. Identifying human host proteins could improve the possibilities to predict the risk of development of acute severe malaria. This will possible enable improved treatment and thereby lead to a decrease in mortality of malaria infected children. Furthermore, discovering host proteins with altered levels during active infection could generate leads to better understand host-parasite interaction.ResultsHere, we have analyzed a total of 541 pediatric plasma samples that were collected from community controls and individuals with mild or severe malaria in Rwanda. Protein profiles of these plasma samples were generated with an antibody-based suspension bead array containing 255 antibodies targeting 115 human proteins. We present 22 proteins with a strong discriminatory capacity (adjusted p-values below 10-19) for separating malaria cases from community controls. This panel of proteins contains among others acute phase proteins and proteins connected to cell adhesion and migration. Among these, three proteins showed lower plasma levels in the group of malaria-infected individuals compared to the control group. One of these proteins is the anti-adhesive secreted protein acidic and cysteine rich (SPARC) with possible connections to parasite cytoadhesion. A multi-protein panel of six proteins, including SPARC, could differentiate between controls and malaria cases with an AUC of 0.98. Furthermore, a panel of 37 proteins, including proteins associated to erythrocyte membranes, was identified as candidates for separation of mild and severe malaria patients (adjusted pvalues below 0.05).ConclusionThe herein identified set of human proteins has a significant discriminatory capacity between community controls and malaria cases. We also present proteins offering the possibility to enable stratification and risk prediction for the development of severe malaria. This constitutes an important set that could enable enhanced understanding and thereby also possibilities for better treatment of acute severe pediatric malaria.
|
|
| 13. |
- Reuterswärd, Philippa, et al.
(författare)
-
Levels of human proteins in plasma associated with acute paediatric malaria
- 2018
-
Ingår i: Malaria Journal. - : BMC. - 1475-2875. ; 17
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The intimate interaction between the pathophysiology of the human host and the biology of the Plasmodium falciparum parasite results in a wide spectrum of disease outcomes in malaria. Development of severe disease is associated with a progressively augmented imbalance in pro- and anti-inflammatory responses to high parasite loads and sequestration of parasitized erythrocytes. Although these phenomena collectively constitute common denominators for the wide variety of discrete severe malaria manifestations, the mechanistic rationales behind discrepancies in outcome are poorly understood. Exploration of the human pathophysiological response by variations in protein profiles in plasma presents an excellent opportunity to increase the understanding. This is ultimately required for better prediction, prevention and treatment of malaria, which is essential for ongoing elimination and eradication efforts. Results: An affinity proteomics approach was used to analyse 541 paediatric plasma samples collected from community controls and patients with mild or severe malaria in Rwanda. Protein profiles were generated with an antibody-based suspension bead array containing 255 antibodies targetting 115 human proteins. Here, 57 proteins were identified with significantly altered levels (adjusted p-values<0.001) in patients with malaria compared to controls. From these, the 27 most significant proteins (adjusted p-values<10(-14)) were selected for a stringent analysis approach. Here, 24 proteins showed elevated levels in malaria patients and included proteins involved in acute inflammatory response as well as cell adhesion. The remaining three proteins, also implicated in immune regulation and cellular adhesivity, displayed lower abundance in malaria patients. In addition, 37 proteins (adjusted p-values<0.05) were identified with increased levels in patients with severe compared to mild malaria. This set includes, proteins involved in tissue remodelling and erythrocyte membrane proteins. Collectively, this approach has been successfully used to identify proteins both with known and unknown association with different stages of malaria. Conclusion: In this study, a high-throughput affinity proteomics approach was used to find protein profiles in plasma linked to P. falciparum infection and malaria disease progression. The proteins presented herein are mainly involved in inflammatory response, cellular adhesion and as constituents of erythrocyte membrane. These findings have a great potential to provide increased conceptual understanding of host-parasite interaction and malaria pathogenesis.
|
|
| 14. |
- Surowiec, Izabella, et al.
(författare)
-
The oxylipin and endocannabidome responses in acute phase Plasmodium falciparum malaria in children
- 2017
-
Ingår i: Malaria Journal. - : BIOMED CENTRAL LTD. - 1475-2875. ; 16
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Oxylipins and endocannabinoids are low molecular weight bioactive lipids that are crucial for initiation and resolution of inflammation during microbial infections. Metabolic complications in malaria are recognized contributors to severe and fatal malaria, but the impact of malaria infection on the production of small lipid derived signalling molecules is unknown. Knowledge of immunoregulatory patterns of these molecules in malaria is of great value for better understanding of the disease and improvement of treatment regimes, since the action of these classes of molecules is directly connected to the inflammatory response of the organism.Methods: Detection of oxylipins and endocannabinoids from plasma samples from forty children with uncomplicated and severe malaria as well as twenty controls was done after solid phase extraction followed by chromatography mass spectrometry analysis. The stable isotope dilution method was used for compound quantification. Data analysis was done with multivariate (principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA (R)) and univariate approaches (receiver operating characteristic (ROC) curves, t tests, correlation analysis).Results: Forty different oxylipin and thirteen endocannabinoid metabolites were detected in the studied samples, with one oxylipin (thromboxane B2, TXB2) in significantly lower levels and four endocannabinoids (OEA, PEA, DEA and EPEA) at significantly higher levels in infected individuals as compared to controls according to t test analysis with Bonferroni correction. Three oxylipins (13-HODE, 9-HODE and 13-oxo-ODE) were higher in severe compared to uncomplicated malaria cases according to the results from multivariate analysis. Observed changes in oxylipin levels can be connected to activation of cytochrome P450 (CYP) and 5-lipoxygenase (5-LOX) metabolic pathways in malaria infected individuals compared to controls, and related to increased levels of all linoleic acid oxylipins in severe patients compared to uncomplicated ones. The endocannabinoids were extremely responsive to malaria infection with majority of this class of molecules found at higher levels in infected individuals compared to controls.Conclusions: It was possible to detect oxylipin and endocannabinoid molecules that can be potential biomarkers for differentiation between malaria infected individuals and controls and between different classes of malaria. Metabolic pathways that could be targeted towards an adjunctive therapy in the treatment of malaria were also pinpointed.
|
|
| 15. |
- Welén, Karin, 1970, et al.
(författare)
-
A Phase 2 Trial of the Effect of Antiandrogen Therapy on COVID-19 Outcome : No Evidence of Benefit, Supported by Epidemiology and In Vitro Data
- 2022
-
Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 81:3, s. 285-293
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Men are more severely affected by COVID-19. Testosterone may influence SARS-CoV-2 infection and the immune response.Objective: To clinically, epidemiologically, and experimentally evaluate the effect of antiandrogens on SARS-CoV-2 infection.Designs, settings, and participants: A randomized phase 2 clinical trial (COVIDENZA) enrolled 42 hospitalized COVID-19 patients before safety evaluation. We also conducted a population-based retrospective study of 7894 SARS-CoV-2–positive prostate cancer patients and an experimental study using an air-liquid interface three-dimensional culture model of primary lung cells.Intervention: In COVIDENZA, patients were randomized 2:1 to 5 d of enzalutamide or standard of care.Outcome measurements: The primary outcomes in COVIDENZA were the time to mechanical ventilation or discharge from hospital. The population-based study investigated risk of hospitalization, intensive care, and death from COVID-19 after androgen inhibition.Results and limitations: Enzalutamide-treated patients required longer hospitalization (hazard ratio [HR] for discharge from hospital 0.43, 95% confidence interval [CI] 0.20–0.93) and the trial was terminated early. In the epidemiological study, no preventive effects were observed. The frail population of patients treated with androgen deprivation therapy (ADT) in combination with abiraterone acetate or enzalutamide had a higher risk of dying from COVID-19 (HR 2.51, 95% CI 1.52–4.16). In vitro data showed no effect of enzalutamide on virus replication. The epidemiological study has limitations that include residual confounders.Conclusions: The results do not support a therapeutic effect of enzalutamide or preventive effects of bicalutamide or ADT in COVID-19. Thus, these antiandrogens should not be used for hospitalized COVID-19 patients or as prevention for COVID-19. Further research on these therapeutics in this setting are not warranted.Patient summary: We studied whether inhibition of testosterone could diminish COVID-19 symptoms. We found no evidence of an effect in a clinical study or in epidemiological or experimental investigations. We conclude that androgen inhibition should not be used for prevention or treatment of COVID-19.
|
|
| 16. |
- Welen, Karin, et al.
(författare)
-
COVIDENZA - A prospective, multicenter, randomized PHASE II clinical trial of enzalutamide treatment to decrease the morbidity in patients with Corona virus disease 2019 (COVID-19): a structured summary of a study protocol for a randomised controlled trial.
- 2021
-
Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 22:1
-
Tidskriftsartikel (refereegranskat)abstract
- The main goal of the COVIDENZA trial is to evaluate if inhibition of testosterone signalling by enzalutamide can improve the outcome of patients hospitalised for COVID-19. The hypothesis is based on the observation that the majority of patients in need of intensive care are male, and the connection between androgen receptor signalling and expression of TMPRSS2, an enzyme important for SARS-CoV-2 host cell internalization.Hospitalised COVID-19 patients will be randomised (2:1) to enzalutamide plus standard of care vs. standard of care designed to identify superiority.Included participants, men or women above 50 years of age, must be hospitalised for PCR confirmed COVID-19 symptoms and not in need of immediate mechanical ventilation. Major exclusion criteria are breast-feeding or pregnant women, hormonal treatment for prostate or breast cancer, treatment with immunosuppressive drugs, current symptomatic unstable cardiovascular disease (see Additional file 1 for further details). The trial is registered at Umeå University Hospital, Region Västerbotten, Sweden and 8 hospitals are approved for inclusion in Sweden.Patients randomised to the treatment arm will be treated orally with 160 mg (4x40 mg) enzalutamide (Xtandi®) daily, for five consecutive days. The study is not placebo controlled. The comparator is standard of care treatment for patients hospitalised with COVID-19.The primary endpoints of the study are (time to) need of mechanical ventilation or discharge from hospital as assessed by a clinical 7-point ordinal scale (up to 30 days after inclusion).Randomisation was stratified by center and sex. Each strata was randomized separately with block size six with a 2:1 allocation ratio (enzalutamide + "standard of care": "standard of care"). The randomisation list, with consecutive subject numbers, was generated by an independent statistician using the PROC PLAN procedure of SAS version 9.4 software (SAS Institute, Inc, Cary, North Carolina) BLINDING (MASKING): This is an open-label trial.The trial is designed to have three phases. The first, an exploration phase of 45 participants (30 treatment and 15 control) will focus on safety and includes a more extensive laboratory assessment as well as more frequent safety evaluation. The second prolongation phase, includes the first 100 participants followed by an interim analysis to define the power of the study. The third phase is the continuation of the study up to maximum 600 participants included in total.The current protocol version is COVIDENZA v2.0 as of September 10, 2020. Recruitment started July 29, 2020 and is presently in safety pause after the first exploration phase. Recruitment is anticipated to be complete by 31 December 2021.Eudract number 2020-002027-10 ClinicalTrials.gov Identifier: NCT04475601 , registered June 8, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
|
|
| 17. |
- Zalewski, Kamil, et al.
(författare)
-
A call for new communication channels for gynecological oncology trainees : a survey on social media use and educational needs by the European network of young gynecological oncologists
- 2017
-
Ingår i: International Journal of Gynecological Cancer. - 1048-891X .- 1525-1438. ; 27:3, s. 620-626
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of the study was to assess patterns in the use of social media (SM) platforms and to identify the training needs among European gynecologic oncology trainees.METHODS: In 2014, a web-based survey was sent to 633 trainees from the European Network of Young Gynaecological Oncologists (ENYGO) database. The 14-item questionnaire (partially using a 1- to 5-point Likert scale) assessed respondents' use of SM and preference for workshop content and organization. Descriptive analysis was used to describe the mean scores reported for different items, and the internal reliability of the questionnaire was assessed by Cronbach α.RESULTS: In total, 170 ENYGO members (27%) responded to the survey. Of those, 91% said that they use SM platforms, mostly for private purposes. Twenty-three percent used SM professionally and 43% indicated that they would consider SM to be a clinical discussion forum. The respondents said that they would like updates on conferences and professional activities to be shared on SM platforms. Complication management, surgical anatomy, and state of the art in gynecologic oncology were identified as preferred workshops topics. The most frequently indicated hands-on workshops were laparoscopic techniques and surgical anatomy. Consultants attached a higher level of importance to palliative care education and communication training than trainees. The mean duration of the workshop preferred was 2 days.CONCLUSIONS: This report highlights the significance of ENYGO trainees' attachment to SM platforms. Most respondents expect ENYGO to use these online channels for promoting educational activities and other updates. Using SM for clinical discussion will require specific guidelines to secure professional and also consumer integrity. This survey confirms surgical management and the state of the art as important knowledge gaps, and ENYGO has tailored its activities according to these results. Future activities will further direct attention and resources to education in palliative care and molecular tumor biology.
|
|
