| 1. |
- Balestrino, R, et al.
(author)
-
Applications of the European Parkinson's Disease Association sponsored Parkinson's Disease Composite Scale (PDCS)
- 2019
-
In: NPJ Parkinson's disease. - : Springer Science and Business Media LLC. - 2373-8057. ; 5, s. 26-
-
Journal article (peer-reviewed)abstract
- This study was addressed to determine the presence of Parkinson disease (PD) manifestations, their distribution according to motor subtypes, and the relationships with health-related quality of life (QoL) using the recently validated European Parkinson’s Disease Association sponsored Parkinson’s Disease Composite Scale (PDCS). Frequency of symptoms was determined by the scores of items (present if >0). Using ROC analysis and Youden method, MDS-UPDRS motor subtypes were projected on the PDCS to achieve a comparable classification based on the PDCS scores. The same method was used to estimate severity levels from other measures in the study. The association between the PDCS and QoL (PDQ-39) was analyzed by correlation and multiple linear regression. The sample consisted of 776 PD patients. We found that the frequency of PD manifestations with PDCS and MDS-UPDRS were overlapping, the average difference between scales being 5.5% only. Using the MDS-UPDRS subtyping, 215 patients (27.7%) were assigned as Tremor Dominant (TD), 60 (7.7%) Indeterminate, and 501 (64.6%) Postural Instability and Gait Difficulty (PIGD) in this cohort. With this classification as criterion, the analogous PDCS-based ratio provided these cut-off values: TD subtype, ≥1.06; Indeterminate, <1.06 but >0.65; and PIGD, <0.65. The agreement between the two scales on this classification was substantial (87.6%; kappa = 0.69). PDCS total score cut-offs for PD severity were: 23/24 for mild/moderate and 41/42 for moderate/severe. Moderate to high correlations (r = 0.35–0.80) between PDCS and PDQ-39 were obtained, and the four PDCS domains showed a significant independent influence on QoL. The conclusions are: (1) the PDCS assessed the frequency of PD symptoms analogous to the MDS-UPDRS; (2) motor subtypes and severity levels can be determined with the PDCS; (3) a significant association between PDCS and QoL scores exists.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Sjögren, Erik, 1977-, et al.
(author)
-
Clinical testing of three novel transient receptor potential cation channel subfamily V member 1 antagonists in a pharmacodynamic intradermal capsaicin model
- 2018
-
In: European Journal of Pain. - : WILEY. - 1090-3801 .- 1532-2149. ; 22:7, s. 1214-1228
-
Journal article (peer-reviewed)abstract
- Background The transient receptor potential cation channel subfamily V 1 (TRPV1) is involved in nociception and has thus been of interest for drug developers, as a target for novel analgesics. However, several oral TRPV1 antagonists have failed in development, and novel approaches to target TRPV1 with innovative chemistry are needed. Method This work describes an intradermal microdosing approach in humans for pharmacodynamic deductions and pharmacological profiling of compounds. First, a human capsaicin model was developed, to generate pharmacodynamic translational data (Study Part A, n=24). Then, three small molecule TRPV1 antagonists (AZ11760788, AZ12048189 and AZ12099548) were investigated in healthy volunteers (Study Part B, n=36), applying the established model. Pain and flare were assessed by Visual Analogue Score and laser Doppler, respectively. Results The developed model proved useful for pharmacologic deductions; all compounds caused a dose-dependent inhibition of capsaicin-induced pain and flare responses, with a rank order potency of AZ11760788>AZ12048189 >> AZ12099548. In addition, the dose-response data showed that the minimal antagonist concentrations needed to inhibit TRPV1 was 6-7 times the equilibrium dissociation constant for each compound. Conclusion With careful design of a pharmacodynamic translational human pain model, it was possible to rank order TRPV1 efficacy among three investigational TRPV1 antagonists, and to estimate human efficacious concentrations. SignificanceThis fast and cost-effective translational approach allows for generation of human target engagement information early in drug development. This could be of value for other development programmes where pharmacological targets are expressed in peripheral sensory nerves.
|
|
| 6. |
- Thust, S. C., et al.
(author)
-
Glioma imaging in Europe : A survey of 220 centres and recommendations for best clinical practice
- 2018
-
In: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 28:8, s. 3306-3317
-
Journal article (peer-reviewed)abstract
- Objectives: At a European Society of Neuroradiology (ESNR) Annual Meeting 2015 workshop, commonalities in practice, current controversies and technical hurdles in glioma MRI were discussed. We aimed to formulate guidance on MRI of glioma and determine its feasibility, by seeking information on glioma imaging practices from the European Neuroradiology community. Methods: Invitations to a structured survey were emailed to ESNR members (n=1,662) and associates (n=6,400), European national radiologists’ societies and distributed via social media. Results: Responses were received from 220 institutions (59% academic). Conventional imaging protocols generally include T2w, T2-FLAIR, DWI, and pre- and post-contrast T1w. Perfusion MRI is used widely (85.5%), while spectroscopy seems reserved for specific indications. Reasons for omitting advanced imaging modalities include lack of facility/software, time constraints and no requests. Early postoperative MRI is routinely carried out by 74% within 24–72 h, but only 17% report a percent measure of resection. For follow-up, most sites (60%) issue qualitative reports, while 27% report an assessment according to the RANO criteria. A minority of sites use a reporting template (23%). Conclusion: Clinical best practice recommendations for glioma imaging assessment are proposed and the current role of advanced MRI modalities in routine use is addressed. Key Points: • We recommend the EORTC-NBTS protocol as the clinical standard glioma protocol.• Perfusion MRI is recommended for diagnosis and follow-up of glioma.• Use of advanced imaging could be promoted with increased education activities.• Most response assessment is currently performed qualitatively.• Reporting templates are not widely used, and could facilitate standardisation.
|
|
| 7. |
- Broitman, E., et al.
(author)
-
Mechanical and tribological properties of CNx films deposited by reactive magnetron sputtering
- 2001
-
In: Wear. - 0043-1648 .- 1873-2577. ; 248:1-2, s. 55-64
-
Journal article (peer-reviewed)abstract
- The hardness, elasticity, wear rate and friction coefficient of carbon nitride (CNx) films of defined microstructure and composition are presented. CNx films were deposited by dc reactive magnetron sputtering from a C target in N2/Ar plasma. Films were grown on Si (001), Ni, and HSS substrates to thickness of ~0.5 µm at a total pressure of 3 mTorr with the N2 fraction varied from 0 to 1, and the substrate temperature Ts, varied from ambient to 350°C. The mechanical and tribological properties of the coatings were evaluated by nanoindentation and dry ball-on-disk test. For CNx (0 = x = 0.35) films deposited below 200°C (amorphous structure), the elastic recovery and hardness do not change significantly with increasing N concentration, however, the friction coefficient increases from 0.19 to 0.45, while the coating wear rate is low. For CNx (0 = x = 0.15) films grown at Ts = 350°C, where a transition from a graphite-like to a "fullerene-like" phase occurs, a dramatic increase in hardness and elasticity is observed. Furthermore, the rms surface roughness decreases from 15.0 to 0.4 nm. For 0.15 = x = 0.20, CNx films deposited at Ts = 350°C (fullerene-like phase) exhibit a smooth surface, high hardness and elasticity (~90% recovery), and a coefficient of friction against hard steel of ~0.25. For all substrates, film friction coefficient tends to increase as the nitrogen content in the film is increased. Results also indicate the formation of a transfer layer which improves the tribological properties of the films. © 2001 Elsevier Science B.V. All rights reserved.
|
|
| 8. |
- Coorevits, Pascal, et al.
(author)
-
Electronic health records : new opportunities for clinical research
- 2013
-
In: Journal of Internal Medicine. - : Wiley-Blackwell. - 0954-6820 .- 1365-2796. ; 274:6, s. 547-60
-
Journal article (peer-reviewed)abstract
- Clinical research is on the threshold of a new era in which electronic health records (EHRs) are gaining an important novel supporting role. Whilst EHRs used for routine clinical care have some limitations at present, as discussed in this review, new improved systems and emerging research infrastructures are being developed to ensure that EHRs can be used for secondary purposes such as clinical research, including the design and execution of clinical trials for new medicines. EHR systems should be able to exchange information through the use of recently published international standards for their interoperability and clinically validated information structures (such as archetypes and international health terminologies), to ensure consistent and more complete recording and sharing of data for various patient groups. Such systems will counteract the obstacles of differing clinical languages and styles of documentation as well as the recognized incompleteness of routine records. Here, we discuss some of the legal and ethical concerns of clinical research data reuse and technical security measures that can enable such research while protecting privacy. In the emerging research landscape, cooperation infrastructures are being built where research projects can utilize the availability of patient data from federated EHR systems from many different sites, as well as in international multilingual settings. Amongst several initiatives described, the EHR4CR project offers a promising method for clinical research. One of the first achievements of this project was the development of a protocol feasibility prototype which is used for finding patients eligible for clinical trials from multiple sources.
|
|
| 9. |
- Fjalldal, S., et al.
(author)
-
Detailed assessment of hypothalamic damage in craniopharyngioma patients with obesity
- 2019
-
In: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 43:3, s. 533-544
-
Journal article (peer-reviewed)abstract
- Background/objectives: Hypothalamic obesity (HO) occurs in 50% of patients with the pituitary tumor craniopharyngioma (CP). Attempts have been made to predict the risk of HO based on hypothalamic (HT) damage on magnetic resonance imaging (MRI), but none have included volumetry. We performed qualitative and quantitative volumetric analyses of HT damage. The results were explored in relation to feeding related peptides and body fat. Subjects/methods: A cross-sectional study of childhood onset CPs involving 3 Tesla MRI, was performed at median 22 years after first operation; 41 CPs, median age 35 (range: 17–56), of whom 23 had HT damage, were compared to 32 controls. After exclusions, 35 patients and 31 controls remained in the MRI study. Main outcome measures were the relation of metabolic parameters to HT volume and qualitative analyses of HT damage. Results: Metabolic parameters scored persistently very high in vascular risk particularly among HT damaged patients. Patients had smaller HT volumes compared to controls 769 (35–1168) mm3 vs. 879 (775–1086) mm3; P < 0.001. HT volume correlated negatively with fat mass and leptin among CP patients (rs = −0.67; P <.001; rs = −0.53; P = 0.001), and explained 39% of the variation in fat mass. For every 100 mm3 increase in HT volume fat mass decreased by 2.7 kg (95% CI: 1.5–3.9; P < 0.001). Qualitative assessments revealed HT damage in three out of six patients with normal volumetry, but HT damage according to operation records. Conclusions: A decrease in HT volume was associated with an increase in fat mass and leptin. We present a method with a high inter-rater reliability (0.94) that can be applied by nonradiologists for the assessment of HT damage. The method may be valuable in the risk assessment of diseases involving the HT.
|
|
| 10. |
- Fjalldal, S., et al.
(author)
-
Microstructural white matter alterations and hippocampal volumes are associated with cognitive deficits in craniopharyngioma
- 2018
-
In: European Journal of Endocrinology. - : BIOSCIENTIFICA LTD. - 0804-4643 .- 1479-683X. ; 178:6, s. 577-587
-
Journal article (peer-reviewed)abstract
- Context: Patients with craniopharyngioma (CP) and hypothalamic lesions (HL) have cognitive deficits. Which neural pathways are affected is unknown. Objective: To determine whether there is a relationship between microstructural white matter (WM) alterations detected with diffusion tensor imaging (DTI) and cognition in adults with childhood-onset CP. Design: A cross-sectional study with a median follow-up time of 22 (6-49) years after operation. Setting: The South Medical Region of Sweden (2.5 million inhabitants). Participants: Included were 41 patients (24 women, amp;gt;= 17 years) surgically treated for childhood-onset CP between 1958-2010 and 32 controls with similar age and gender distributions. HI was found in 23 patients. Main outcome measures: Subjects performed cognitive tests and magnetic resonance imaging, and images were analyzed using DTI of uncinate fasciculus, fornix, cingulum, hippocampus and hypothalamus as well as hippocampal volumetry. Results: Right uncinate fasciculus was significantly altered (P amp;lt;= 0.01) Microstructural WM alterations in left ventral cingulum were significantly associated with worse performance in visual episodic memory, explaining approximately 50% of the variation. Alterations in dorsal cingulum were associated with worse performance in immediate, delayed recall and recognition, explaining 26-38% of the variation, and with visuospatial ability and executive function, explaining 19-29%. Patients who had smaller hippocampal volume had worse general knowledge (P = 0.028), and microstructural WM alterations in hippocampus were associated with a decline in general knowledge and episodic visual memory. Conclusions: A structure to function relationship is suggested between microstructural WM alterations in cingulum and in hippocampus with cognitive deficits in CP.
|
|
