| 1. |
- Mercuri, E., et al.
(författare)
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Safety and effectiveness of ataluren: comparison of results from the STRIDE Registry and CINRG DMD Natural History Study
- 2020
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Ingår i: Journal of Comparative Effectiveness Research. - : Becaris Publishing Limited. - 2042-6305 .- 2042-6313. ; 9:5, s. 341-360
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Strategic Targeting of Registries and International Database of Excellence (STRIDE) is an ongoing, multicenter registry providing real-world evidence regarding ataluren use in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD). We examined the effectiveness of ataluren + standard of care (SoC) in the registry versus SoC alone in the Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study (DNHS), DMD genotype-phenotype/-ataluren benefit correlations and ataluren safety. Patients & methods: Propensity score matching was performed to identify STRIDE and CINRG DNHS patients who were comparable in established disease progression predictors (registry cut-off date, 9 July 2018). Results & conclusion: Kaplan-Meier analyses demonstrated that ataluren + SoC significantly delayed age at loss of ambulation and age at worsening performance in timed function tests versus SoC alone (p <= 0.05). There were no DMD genotype-phenotype/ataluren benefit correlations. Ataluren was well tolerated. These results indicate that ataluren + SoC delays functional milestones of DMD progression in patients with nmDMD in routine clinical practice. ClinicalTrials.gov identifier: NCT02369731. ClinicalTrials.gov identifier: NCT02369731.
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| 2. |
- Haridass, Isha N., et al.
(författare)
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Cellular metabolism and pore lifetime of human skin following microprojection array mediation
- 2019
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Ingår i: Journal of Controlled Release. - : ELSEVIER SCIENCE BV. - 0168-3659 .- 1873-4995. ; 306, s. 59-68
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Tidskriftsartikel (refereegranskat)abstract
- Skin-targeting microscale medical devices are becoming popular for therapeutic delivery and diagnosis. We used cryo-SEM, fluorescence lifetime imaging microscopy (FLIM), autofluorescence imaging microscopy and inflammatory response to study the puncturing and recovery of human skin ex vivo and in vivo after discretised puncturing by a microneedle array (Nanopatch (R)). Pores induced by the microprojections were found to close by similar to 25% in diameter within the first 30 min, and almost completely close by similar to 6 h. FLIM images of ex vivo viable epidermis showed a stable fluorescence lifetime for unpatched areas of similar to 1000 ps up to 24 h. Only the cells in the immediate puncture zones (in direct contact with projections) showed a reduction in the observed fluorescence lifetimes to between similar to 518-583 ps. The ratio of free-bound NAD(P)H (alpha 1/alpha 2) in unaffected areas of the viable epidermis was similar to 2.5-3.0, whereas the ratio at puncture holes was almost double at similar to 4.2-4.6. An exploratory pilot in vivo study also suggested similar closure rate with histamine administration to the forearms of human volunteers after Nanopatch (R) treatment, although a prolonged inflammation was observed with Tissue Viability Imaging. Overall, this work shows that the pores created by the microneedle-type medical device, Nanopatch (R), are transient, with the skin recovering rapidly within 1-2 days in the epidermis after application.
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| 3. |
- Henricson, E. K., et al.
(författare)
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The cooperative international neuromuscular research group Duchenne natural history study: Glucocorticoid treatment preserves clinically meaningful functional milestones and reduces rate of disease progression as measured by manual muscle testing and other commonly used clinical trial outcome measures
- 2013
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Ingår i: Muscle & Nerve. - : Wiley. - 0148-639X. ; 48:1, s. 55-67
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Glucocorticoid (GC) therapy in Duchenne muscular dystrophy (DMD) has altered disease progression, necessitating contemporary natural history studies. Methods: The Cooperative Neuromuscular Research Group (CINRG) DMD Natural History Study (DMD-NHS) enrolled 340 DMD males, ages 2-28 years. A comprehensive battery of measures was obtained. Results: A novel composite functional milestone scale scale showed clinically meaningful mobility and upper limb abilities were significantly preserved in GC-treated adolescents/young adults. Manual muscle test (MMT)-based calculations of global strength showed that those patients <10 years of age treated with steroids declined by 0.4 +/- 0.39 MMT unit/year, compared with -0.4 +/- 0.39 MMT unit/year in historical steroid-naive subjects. Pulmonary function tests (PFTs) were relatively preserved in steroid-treated adolescents. The linearity and magnitude of decline in measures were affected by maturational changes and functional status. Conclusions: In DMD, long-term use of GCs showed reduced strength loss and preserved functional capabilities and PFTs compared with previous natural history studies performed prior to the widespread use of GC therapy.
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| 4. |
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| 5. |
- Matilda, E., et al.
(författare)
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Preoperative peripheral and core temperature : an observational study at a day-surgery unit
- 2020
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Ingår i: British Journal of Nursing. - : NLM (Medline). - 0966-0461 .- 2052-2819. ; 29:3, s. 160-164
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Hypothermia is a common problem in the surgical context and can lead to serious consequences for the patient and increased costs for society.AIMS:To study day-surgery patients' peripheral and core temperatures during the preoperative phase.METHODS:In total, 50 day-surgery patients participated in the study. Two sets of measurements of temperatures were made: core temperature and peripheral temperatures (two measuring points on the upper body and lower extremities respectively) were measured on arrival at the day-surgery unit, as well as on arrival at the operating theatre. The data were normally distributed and a paired t-test was used for statistical analysis.FINDINGS:Peripheral temperatures had significant changes, with measuring points on the upper body decreasing and measuring points on the lower extremities increasing in temperature. The results show no significant change in core temperature.CONCLUSION:The measurements show that 28% of the patients were below recommended preoperative temperature on arrival at the operating theatre. Further research is needed to study the development of body temperature perioperatively as well as at what point reheating interventions should be introduced.
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| 6. |
- Mercuri, E., et al.
(författare)
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Safety and effectiveness of ataluren in patients with nonsense mutation DMD in the STRIDE Registry compared with the CINRG Duchenne Natural History Study (2015-2022): 2022 interim analysis
- 2023
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Ingår i: Journal of Neurology. - 0340-5354. ; 270, s. 3896-3913
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveStrategic Targeting of Registries and International Database of Excellence (STRIDE) is an ongoing, international, multicenter registry of real-world ataluren use in individuals with nonsense mutation Duchenne muscular dystrophy (nmDMD) in clinical practice. This updated interim report (data cut-off: January 31, 2022), describes STRIDE patient characteristics and ataluren safety data, as well as the effectiveness of ataluren plus standard of care (SoC) in STRIDE versus SoC alone in the Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study (DNHS).MethodsPatients are followed up from enrollment for at least 5 years or until study withdrawal. Propensity score matching was performed to identify STRIDE and CINRG DNHS patients who were comparable in established predictors of disease progression.ResultsAs of January 31, 2022, 307 patients were enrolled from 14 countries. Mean (standard deviation [SD]) ages at first symptoms and at genetic diagnosis were 2.9 (1.7) years and 4.5 (3.7) years, respectively. Mean (SD) duration of ataluren exposure was 1671 (56.8) days. Ataluren had a favorable safety profile; most treatment-emergent adverse events were mild or moderate and unrelated to ataluren. Kaplan-Meier analyses demonstrated that ataluren plus SoC significantly delayed age at loss of ambulation by 4 years (p < 0.0001) and age at decline to %-predicted forced vital capacity of < 60% and < 50% by 1.8 years (p = 0.0021) and 2.3 years (p = 0.0207), respectively, compared with SoC alone.ConclusionLong-term, real-world treatment with ataluren plus SoC delays several disease progression milestones in individuals with nmDMD. NCT02369731; registration date: February 24, 2015.
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| 7. |
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| 8. |
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| 9. |
- Droog Tesselaar, Erik, et al.
(författare)
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A protocol for iontophoresis of acetylcholine and sodium nitroprusside that minimises nonspecific vasodilatory effects
- 2004
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Ingår i: Microvascular research. - : Elsevier BV. - 0026-2862. ; 67:2, s. 197-202
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Tidskriftsartikel (refereegranskat)abstract
- Iontophoresis of vasoactive substances is a promising tool for studying pharmacological aspects of the (patho)physiology of the microvasculature. However, nonspecific microvascular responses are a common problem in most protocols used. We studied the effect of current density (mA/cm2), charge density (mC/cm2), drug concentration (mass %) and vehicle concentration (M) on the nonspecific vasodilatation during iontophoresis of sodium chloride, acetylcholine (ACh) and sodium nitroprusside (SNP). We found that nonspecific vasodilatation depended on current density and charge density in both anodal and cathodal iontophoresis. The responses to ACh and SNP were dependent on current density, charge density and drug concentration. We found that by limiting current density (<0.01 mA/cm2) and charge density (<7.8 mC/cm2) and with adjusted concentrations for drugs and vehicles, it is possible to prevent nonspecific effects during iontophoresis of ACh and SNP, while maximum drug effects (plateaus in the dose–response curves) are still obtained. These new findings are important for future iontophoresis studies in which vasoactive drugs are used to assess microvascular function because the presented approach has advantages compared to older techniques, which mainly have attempted to suppress or compensate for the nonspecific responses during iontophoresis by the use of local anaesthetics or the measurement of drug-minus-vehicle responses, both of which present well-known experimental shortcomings.
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| 10. |
- Kamrad, Ilka, et al.
(författare)
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Good outcome scores and high satisfaction rate after primary total ankle replacement : 167 patients followed for 24 months in the Swedish Ankle Registry
- 2017
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Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 88:6, s. 675-680
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose — Total ankle replacement (TAR) is gaining popularity for treatment of end-stage ankle arthritis. Large patient-centered outcome studies are, however, few. Here, we report data from the Swedish Ankle Registry. Patients and methods — We examined outcomes after primary TAR in patients from the Swedish Ankle Registry using PROMs (Patient Reported Outcome Measures; generic: EQ-5D and SF-36, region specific: SEFAS (Self-Reported Foot and Ankle Score), and a question on satisfaction). We included 241 patients registered with primary TAR between 2008 and 2016 and who completed PROMs preoperatively and postoperatively up to 24 months. We evaluated changes in PROMs following surgery and estimated effects of age, diagnosis, prosthetic design, and preoperative functional score on the outcomes. Results — All absolute scores improved from preoperative to 24 months after surgery (p ≤ 0.001). 71% of the patients were satisfied or very satisfied at the latest follow-up and 12% dissatisfied or very dissatisfied. Postoperative SEFAS correlated with age (r = 0.2, p = 0.01) and preoperative SEFAS (r = 0.3, p < 0.001), as did patient satisfaction (r = −0.2; p ≤ 0.03). Postoperative SEFAS and EQ-5D were similar between different diagnoses or prosthetic designs. Preoperative SF-36 was associated with diagnosis (p ≤ 0.03), postoperative SF-36 with age (r = 0.2, p = 0.01) and diagnosis (p < 0.03). Interpretation — We found statistically and clinically significant improvements in patient-reported outcomes following TAR surgery. The postoperative region-specific SEFAS was positively associated with older age. Prosthetic design seemed not to influence patient-reported outcome, whereas diagnosis partly did. Studies with longer follow-up are necessary to establish the long-term outcome of TAR and to elucidate whether short- and mid-term outcomes may predict implant failure.
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| 11. |
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| 12. |
- Mernelius, S., et al.
(författare)
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Staphylococcus aureus colonization related to severity of hand eczema
- 2016
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Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - : Springer. - 0934-9723 .- 1435-4373. ; 35:8, s. 1355-1361
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge on Staphylococcus aureus colonization rates and epidemiology in hand eczema is limited. The aim of this study was to clarify some of these issues. Samples were collected by the "glove juice" method from the hands of 59 patients with chronic hand eczema and 24 healthy individuals. Swab samples were taken from anterior nares and throat from 43 of the 59 patients and all healthy individuals. S. aureus were spa typed and analysed by DNA-microarray-based genotyping. The extent of the eczema was evaluated by the hand eczema extent score (HEES). The colonization rate was higher on the hands of hand eczema patients (69 %) compared to healthy individuals (21 %, p amp;lt; 0.001). This was also seen for bacterial density (p = 0.002). Patients with severe hand eczema (HEES a parts per thousand yen 13) had a significantly higher S. aureus density on their hands compared to those with milder eczema (HEES = 1 to 12, p = 0.004). There was no difference between patients and healthy individuals regarding colonization rates in anterior nares or throat. spa typing and DNA-microarray-based genotyping indicated certain types more prone to colonize eczematous skin. Simultaneous colonization, in one individual, with S. aureus of different types, was identified in 60-85 % of the study subjects. The colonization rate and density indicate a need for effective treatment of eczema and may have an impact on infection control in healthcare.
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| 13. |
- O'Doherty, Jim, et al.
(författare)
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Tissue viability imaging (TiVi) in the assessment of divergent beam UV-B provocation
- 2011
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Ingår i: Archives of Dermatological Research. - : Springer. - 0340-3696 .- 1432-069X. ; 303:2, s. 79-87
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Tidskriftsartikel (refereegranskat)abstract
- In routine clinical phototesting and in basic research, naked eye dermatological assessment is the "gold standard" for determining the patient's minimal erythemal dose (MED). In UV-B testing with a divergent, radially attenuating beam of characterised dosimetry, laser Doppler perfusion imaging has been previously used to give quantitative description of reactivity to doses above the MED in addition to a "single-dose" objective determination of the MED itself. In the present paper, the recently developed tissue viability imaging (TiVi) technology is presented for the first time as a reliable, easily applicable, high-resolution alternative to LDPI in the divergent beam testing concept. Data obtained after provocation with a range of doses was analysed in order to determine the reaction diameter, which can be related to the MED using field dosimetry. The dose-response features of exposure above the MED and the relationship between naked eye readings and the diameter were determined from the image data. TiVi data were obtained faster than LDPI data and at a higher spatial resolution of 100 μm instead of 1 mm. A tool was developed to centre over the erythema area of the acquired image. Response data could be plotted continuously against dose. Thresholding of processed images compared to naked eye "gold standard" readings showed that the normal skin value +4 standard deviations produced a good fit between both methods. A linear fitting method for the dose-response data provided a further method of determination of the reaction diameter (MED). Erythemal "volume under the surface (VUS)" for the reaction provided a new concept for visualising information. TiVi offers advantages over LDPI in the acquisition and analysis of data collected during divergent beam testing. An increased amount of data compared to traditional phototesting is easily and more objectively obtained which increases applicability in the clinical and research environment.
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| 14. |
- Toll John, Rani, et al.
(författare)
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Reflectance spectroscopy : to shed new light on the capillary refill test
- 2018
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Ingår i: Journal of Biophotonics. - : Wiley-VCH Verlagsgesellschaft. - 1864-063X .- 1864-0648. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- To use Bioengineering methodology is used to achieve, at five anatomical sites, a detailed, quantitative assessment of the return of blood content to the blanched area, during the Capillary Refill (CR) test. An observational, non-randomized, experimental study on 23 healthy subjects (14 females) was performed in our climate controlled skin physiology laboratory. Our main outcome measures were based on the chronological assessment and quantification of red blood cell concentration (RBC) after the release of blanching pressure in the CR test, using Tissue Viability Imaging (TiVi), a digital photographic technique based on polarisation spectroscopy. TiVi enabled collection of detailed data on skin RBC concentration during the CR test. The results were shown as curves with skin blood concentration (TiVi-value) on the y-axis and the time on the x-axis. Quantitative CR responses showed site and temperature variability. We also suggest possible objective endpoint values from the capillary refill curve. Detailed data on skin RBC concentration during the CR test is easily obtained and allows objective determination of end points not possible to achieve by naked eye assessment. These findings have the potential to place the utility of the CR test in a clinical setting in a new light. Picture: Regular photograph and TiVi Image showing CR test and corresponding graph for the CR response. [GRAPHICS] .
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| 15. |
- Undén, Alexandra, et al.
(författare)
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Better implant survival with modern ankle prosthetic designs : 1,226 total ankle prostheses followed for up to 20 years in the Swedish Ankle Registry
- 2020
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Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 91:2, s. 191-196
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose — We have previously reported on the prosthetic survival of total ankle replacements (TAR) in Sweden performed between 1993 and 2010. Few other reports have been published on 5- and 10-year survival rates. Furthermore, there is a lack of long-term outcome data on modern prosthetic designs. Therefore, we compared early and current prosthetic designs after a mean 7-year follow-up. Patients and methods — On December 31, 2016, 1,230 primary TARs had been reported to the Swedish Ankle Registry. We analyzed prosthetic survival, using exchange or permanent extraction of components as endpoint for 1,226 protheses with mean follow-up of 7 years (0–24). Differences between current (Hintegra, Mobility, CCI, Rebalance, and TM Ankle) and early prosthetic designs (STAR, BP, and AES) were examined by log rank test. Results — 267/1,226 prostheses (22%) had been revised by December 31, 2016. We found an overall prosthetic survival rate at 5 years of 0.85 (95% CI 0.83–0.87), at 10 years 0.74 (CI 0.70–0.77), at 15 years 0.63 (CI 0.58–0.67), and at 20 years 0.58 (CI 0.52–0.65). For early prosthetic designs the 5- and 10-year survival rates were 0.81 (CI 0.78–0.84) and 0.69 (CI 0.64-0.73) respectively, while the corresponding rates for current designs were 0.88 (CI 0.85–0.91) and 0.84 (CI 0.79–0.88). Current prosthetic designs had better survival (log rank test p < 0.001). Interpretation — Our results point to a positive time trend of prosthetic survival in Sweden; use of current prosthetic designs was associated with better prosthetic survival. Improved designs and instrumentation, more experienced surgeons, and improved patient selection may all have contributed to the better outcome.
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