| 1. |
- Bergman, Erik, et al.
(författare)
-
A natural language processing approach towards harmonisation of European medicinal product information
- 2022
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:10
-
Tidskriftsartikel (refereegranskat)abstract
- Product information (PI) is a vital part of any medicinal product approved for use within the European Union and consists of a summary of products characteristics (SmPC) for healthcare professionals and package leaflet (PL) for patients, together with the product packaging. In this study, based on the English corpus of the EMA product information documents for all centrally approved medicinal products within the EU, a BERT sentence embedding model was used together with clustering and dimensional reduction techniques to identify sentence similarity clusters that could be candidates for standardization. A total of 1258 medicinal products were included in the study. From these, a total of 783 K sentences were extracted from SmPC and PL documents which were aggregated into a total of 284 and 129 semantic similarity clusters, respectively. The spread distribution among clusters shows separation into different cluster types. Examples of clusters with low spread include those with identical word embeddings due to current standardization, such as section headings and standard phrases. Others show minor linguistic variations, while the group with the largest variability contains variable wording but with significant semantic overlap. The sentence clusters identified could serve as candidates for further standardization of the PI. Moving from free text human wording to auto-generated text elements based on multiple-choice input for appropriate parts of the package leaflet and summary of product characteristics, could reduce both time and complexity for applicants as well as regulators, and ultimately provide patients and prescribers with documents that are easier to understand and better adapted for search availabilities.
|
|
| 2. |
- Cunningham, Janet, et al.
(författare)
-
Antibody Responses to Severe Acute Respiratory Syndrome Coronavirus 2 in the Serum and Cerebrospinal Fluid of Patients With Coronavirus Disease 2019 and Neurological Symptoms
- 2022
-
Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 225:6, s. 965-970
-
Tidskriftsartikel (refereegranskat)abstract
- Antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in serum and cerebrospinal fluid (CSF) samples from 16 patients with coronavirus disease 2019 and neurological symptoms were assessed using 2 independent methods. Immunoglobulin G (IgG) specific for the virus spike protein was found in 81% of patients in serum and in 56% in CSF. SARS-CoV-2 IgG in CSF was observed in 2 patients with negative serological findings. Levels of IgG in both serum and CSF were associated with disease severity (P < .05). All patients with elevated markers of central nervous system damage in CSF also had CSF antibodies (P = .002), and CSF antibodies had the highest predictive value for neuronal damage markers of all tested clinical variables.
|
|
| 3. |
- Fällmar, David, et al.
(författare)
-
The extent of neuroradiological findings in COVID-19 shows correlation with blood biomarkers, Glasgow coma scale score and days in intensive care
- 2022
-
Ingår i: Journal of neuroradiology. - : Elsevier. - 0150-9861 .- 1773-0406. ; 49:6, s. 421-427
-
Tidskriftsartikel (refereegranskat)abstract
- Background and purposeA wide range of neuroradiological findings has been reported in patients with coronavirus disease 2019 (COVID-19), ranging from subcortical white matter changes to infarcts, haemorrhages and focal contrast media enhancement. These have been descriptively but inconsistently reported and correlations with clinical findings and biomarkers have been difficult to extract from the literature. The purpose of this study was to quantify the extents of neuroradiological findings in a cohort of patients with COVID-19 and neurological symptoms, and to investigate correlations with clinical findings, duration of intensive care and biomarkers in blood.Material and methodsPatients with positive SARS-CoV-2 and at least one new-onset neurological symptom were included from April until July 2020. Nineteen patients were examined regarding clinical symptoms, biomarkers in blood and MRI of the brain. In order to quantify the MRI findings, a semi-quantitative neuroradiological severity scale was constructed a priori, and applied to the MR images by two specialists in neuroradiology.Results and conclusionsThe score from the severity scale correlated significantly with blood biomarkers of CNS injury (glial fibrillary acidic protein, total-tau, ubiquitin carboxyl-terminal hydrolase L1) and inflammation (C-reactive protein), Glasgow Coma Scale score, and the number of days spent in intensive care. The underlying radiological assessments had inter-rater agreements of 90.5%/86% (for assessments with 2/3 alternatives). Total intraclass correlation was 0.80.Previously reported neuroradiological findings in COVID-19 have been diverse and heterogenous. In this study, the extent of findings in MRI examination of the brain, quantified using a structured report, shows correlation with relevant biomarkers.
|
|
| 4. |
- Imlay, Hannah, et al.
(författare)
-
Consensus Definitions of BK Polyomavirus Nephropathy in Renal Transplant Recipients for Clinical Trials
- 2022
-
Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 75:7, s. 1210-1216
-
Tidskriftsartikel (refereegranskat)abstract
- Background BK polyomavirus (BKPyV) infection and BK polyomavirus nephropathy (BKPyVAN) are important causes of allograft dysfunction and premature allograft loss in renal transplant recipients. Results and Discussion Controlled clinical trials to evaluate new agents for prevention and treatment are needed but are hampered by the lack of outcome measures that accurately assess the effect of the intervention, are clinically relevant, and are acceptable from a regulatory perspective. Methods To facilitate consistent end points in clinical trials and to support clinical research and drug development, definitions of BKPyV infection and disease have been developed by the BK Disease Definitions Working Group of the Transplantation Associated Virus Infection Forum with the Forum for Collaborative Research, which consists of scientists, clinicians, regulators, and industry representatives. Conclusions These definitions refine established principles of "proven" BKPyV disease and introduce a "probable" disease category that could be used in clinical trials to prevent or treat BKPyVAN in renal transplant recipients. Standardized BK polyomavirus nephropathy (BKPyVAN) definitions are needed to evaluate therapeutics. We refine established criteria for "proven" BKPyVAN and introduce a "probable disease" category based on allograft dysfunction and plasma DNAemia. Plasma DNAemia thresholds for BKPyVAN are needed.
|
|
| 5. |
- Lorant, Camilla, et al.
(författare)
-
Risk Factors for Developing BK Virus-Associated Nephropathy : A Single-Center Retrospective Cohort Study of Kidney Transplant Recipients
- 2022
-
Ingår i: Annals of Transplantation. - 1425-9524 .- 2329-0358. ; 27
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND BK virus (BKV) infection after kidney transplantation leads to BKV-associated nephropathy (BKVAN) in up to 10% of recipients, and is associated with an increased risk of allograft dysfunction or loss. The objective of this study was to estimate the incidence of BKVAN and to analyze whether enhanced induction is associated with an increased risk of BKVAN, possibly justifying more intensive surveillance.MATERIAL AND METHODS This was a single-center retrospective cohort study. All patients who underwent kidney transplantation or simultaneous pancreas and kidney transplantation at the Uppsala University Hospital in Sweden between 2005 and 2014 were included, a period when BKV screening was not yet implemented. The effect of enhanced induction, defined as treatment with thymoglobulin, rituximab, and/or eculizumab, often in combination with IVIg and glycosorb, immunoadsorption and/or plasmapheresis/apheresis, was analyzed in a multivariable Cox proportional hazards model together with sex, age, cytomegalovirus mismatch (donor+/recipient-) and rejection treatment as co-predictors. Further, the effects of BKVAN on graft survival was analyzed in a univariable Cox proportional hazards model.RESULTS In total 44 of 928 (4.7%) patients developed a biopsy-verified BKVAN 4.8 (1.5-34.2) months after transplantation. Male sex was identified as a risk factor (HR 2.02, P=0.04) but not enhanced induction. Patients with BKVAN experienced a significantly higher risk of graft loss (HR 4.37, P<0.001).CONCLUSIONS Male sex, but not enhanced induction, was found to be a risk factor for BKVAN development after kidney transplantation. BKVAN is associated with an increased risk of graft loss.
|
|
| 6. |
- Westman, Gabriel, 1977-, et al.
(författare)
-
Epilepsy diagnosis after Covid-19: A population-wide study
- 2022
-
Ingår i: Seizure-European Journal of Epilepsy. - : Elsevier BV. - 1059-1311 .- 1532-2688. ; 101, s. 11-14
-
Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to investigate whether SARS-CoV-2 infection was associated with an increased risk of incident epilepsy. Methods: National register-based matched study. Verified cases of SARS-CoV-2 infection were acquired from the system for communicable disease surveillance in Sweden (SmiNet) and linked to data from the National Patient Register (NPR) and Cause of Death register in Sweden. Cases and non-infected controls were compared using a Cox proportional hazards model. Results: A total of 1,221,801 SARS-CoV-2 infected patients and 1,223,312 controls were included. Infection was not associated with an increased risk of epilepsy on a whole population level (HR 1.01, 95% CI 0.92-1.12). Statistically significant effects were observed in patients between 61 and 80 years (HR 1.66, 95% CI 1.37-2.02), also when adjusting for stroke, traumatic brain injury, tumours (same age group HR 1.50, 95% CI 1.24-1.82) and mechanical ventilation (HR 1.28, 95% CI 1.05-1.57). In patients 81-100 years, a similar significant difference was observed (HR 1.77, 95% CI 1.30-2.42), which remained after adjustment for stroke, traumatic brain injury and tumours (HR 1.51, 95% CI 1.10-2.05) but not when mechanical ventilation was included as a covariate (HR 1.34, 95% CI 0.97-1.84). Conclusions: On a whole population level, SARS-CoV-2 infections is not associated with an increased risk of epilepsy. In patients above 60 years, a moderately increased risk of epilepsy was observed. However, considering potential non-controllable bias and that Covid-19 patients in intensive care present with a lower risk than the general ICU population, the virus-induced epileptogenic effect is likely very small.
|
|
| 7. |
|
|
