| 1. |
- Amundstuen Reppe, Linda, et al.
(författare)
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Quality assessment of structure and language elements of written responses given by seven Scandinavian drug information centres
- 2017
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Ingår i: European Journal of Clinical Pharmacology. - : SPRINGER HEIDELBERG. - 0031-6970 .- 1432-1041. ; 73:5, s. 623-631
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to identify structure and language elements affecting the quality of responses from Scandinavian drug information centres (DICs). Six different fictitious drug-related queries were sent to each of seven Scandinavian DICs. The centres were blinded for which queries were part of the study. The responses were assessed qualitatively by six clinical pharmacologists (internal experts) and six general practitioners (GPs, external experts). In addition, linguistic aspects of the responses were evaluated by a plain language expert. The quality of responses was generally judged as satisfactory to good. Presenting specific advice and conclusions were considered to improve the quality of the responses. However, small nuances in language formulations could affect the individual judgments of the experts, e.g. on whether or not advice was given. Some experts preferred the use of primary sources to the use of secondary and tertiary sources. Both internal and external experts criticised the use of abbreviations, professional terminology and study findings that was left unexplained. The plain language expert emphasised the importance of defining and explaining pharmacological terms to ensure that enquirers understand the response as intended. In addition, more use of active voice and less compressed text structure would be desirable. This evaluation of responses to DIC queries may give some indications on how to improve written responses on drug-related queries with respect to language and text structure. Giving specific advice and precise conclusions and avoiding too compressed language and non-standard abbreviations may aid to reach this goal.
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| 2. |
- Amundstuen Reppe, Linda, et al.
(författare)
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Relationship Between Time Consumption and Quality of Responses to Drug-related Queries: A Study From Seven Drug Information Centers in Scandinavia
- 2016
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Ingår i: Clinical Therapeutics. - : ELSEVIER. - 0149-2918 .- 1879-114X. ; 38:7, s. 1738-1749
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The aims of this study were to assess the quality of responses produced by drug information centers (DICs) in Scandinavia, and to study the association between time consumption processing queries and the quality of the responses. Methods: We posed six identical drug-related queries to seven DICs in Scandinavia, and the time consumption required for processing them was estimated. Clinical pharmacologists (internal experts) and general practitioners (external experts) reviewed responses individually. We used mixed model linear regression analyses to study the associations between time consumption on one hand and the summarized quality scores and the overall impression of the responses on the other hand. Findings: Both expert groups generally assessed the quality of the responses as "satisfactory" to "good." A few responses were criticized for being poorly synthesized and less relevant, of which none were quality-assured using co-signatures. For external experts, an increase in time consumption was statistically significantly associated with a decrease in common quality score (change in score, -0.20 per hour of work; 95% CI, -0.33 to -0.06; P = 0.004), and overall impression (change in score, -0.05 per hour of work; 95% CI, -0.08 to -0.01; P = 0.005). No such associations were found for the internal experts assessment. Implications: To our knowledge, this is the first study of the association between time consumption and quality of responses to drug-related queries in DICs. The quality of responses were in general good, but time consumption and quality were only weakly associated in this setting. (C) 2016 The Authors. Published by Elsevier HS Journals, Inc.
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| 3. |
- Astermark, Jan, et al.
(författare)
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Infrastructural considerations of implementing gene therapy for hemophilia in the Nordic context
- 2023
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Ingår i: Therapeutic advances in hematology. - 2040-6207. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite improvements in hemophilia care, challenges remain, including treatment burden and impaired quality of life. Gene therapy may overcome these. However, its introduction presents a challenge. Objectives: To outline a function-based gene therapy working model describing critical milestones associated with gene therapy handling, administration, and follow-up to facilitate and implement an effective infrastructure for gene therapy introduction. Design: Literature review and consensus discussion among Hemophilia Comprehensive Care centers (HCCCs) in the Nordic region. Methods: Representatives from six HCCCs sought to pinpoint milestones and key stakeholders for site readiness at the pre-, peri-, and post-infusion stages, including authority and genetically modified organism (GMO) product requirements, awareness, medical eligibility, logistics and product handling for infusion, laboratory monitoring, and follow-up. Results: A gene therapy transit map was developed with key stakeholders identified. The approach to prepare the vector will differ between the Nordic centers, but the contracted pharmacy unit will be a key stakeholder. Therefore, a pharmacy checklist for the implementation of gene therapy was developed. For the future, Advanced Therapy Medicinal Product centers will also be implemented. Patients’ expectations, commitments, and concerns need to be addressed repeatedly and education of patients and the expanded health-care professionals team will be the key to successful and optimal clinical management. Eligibility testing according to the product’s summary of product characteristics and frequent follow-up and monitoring post-infusion according to the World Federation of Hemophilia chart will be crucial. Conclusion: The approach to deliver gene therapy in the Nordic region will differ partly between the hemophilia centers, but the defined road map with checklists for the implementation of this advanced therapy will be applicable to all. The map may also serve as a platform for the use of future GMO product options both within and outside the area of hemophilia.
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| 4. |
- Broede, Peter, et al.
(författare)
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The Universal Thermal Climate Index UTCI Compared to Ergonomics Standards for Assessing the Thermal Environment
- 2013
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Ingår i: Industrial Health. - 1880-8026. ; 51:1, s. 16-24
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Forskningsöversikt (refereegranskat)abstract
- The growing need for valid assessment procedures of the outdoor thermal environment in the fields of public weather services, public health systems, urban planning, tourism & recreation and climate impact research raised the idea to develop the Universal Thermal Climate Index UTCI based on the most recent scientific progress both in thermo-physiology and in heat exchange theory. Following extensive validation of accessible models of human thermoregulation, the advanced multi-node 'Fiala' model was selected to form the basis of UTCI. This model was coupled with an adaptive clothing model which considers clothing habits by the general urban population and behavioral changes in clothing insulation related to actual environmental temperature. UTCI was developed conceptually as an equivalent temperature. Thus, for any combination of air temperature, wind, radiation, and humidity, UTCI is defined as the air temperature in the reference condition which would elicit the same dynamic response of the physiological model. This review analyses the sensitivity of UTCI to humidity and radiation in the heat and to wind in the cold and compares the results with observational studies and internationally standardized assessment procedures. The capabilities, restrictions and potential future extensions of UTCI are discussed.
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| 5. |
- Bröde, Peter, et al.
(författare)
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Deriving the operational procedure for the Universal Thermal Climate Index (UTCI)
- 2012
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Ingår i: International Journal of Biometeorology. - : Springer Science and Business Media LLC. - 1432-1254 .- 0020-7128. ; 56:3, s. 481-494
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Tidskriftsartikel (refereegranskat)abstract
- The Universal Thermal Climate Index (UTCI) aimed for a one-dimensional quantity adequately reflecting the human physiological reaction to the multi-dimensionally defined actual outdoor thermal environment. The human reaction was simulated by the UTCI-Fiala multi-node model of human thermoregulation, which was integrated with an adaptive clothing model. Following the concept of an equivalent temperature, UTCI for a given combination of wind speed, radiation, humidity and air temperature was defined as the air temperature of the reference environment, which according to the model produces an equivalent dynamic physiological response. Operationalising this concept involved (1) the definition of a reference environment with 50% relative humidity (but vapour pressure capped at 20 hPa), with calm air and radiant temperature equalling air temperature and (2) the development of a one-dimensional representation of the multivariate model output at different exposure times. The latter was achieved by principal component analyses showing that the linear combination of 7 parameters of thermophysiological strain (core, mean and facial skin temperatures, sweat production, skin wettedness, skin blood flow, shivering) after 30 and 120 min exposure time accounted for two-thirds of the total variation in the multi-dimensional dynamic physiological response. The operational procedure was completed by a scale categorising UTCI equivalent temperature values in terms of thermal stress, and by providing simplified routines for fast but sufficiently accurate calculation, which included look-up tables of pre-calculated UTCI values for a grid of all relevant combinations of climate parameters and polynomial regression equations predicting UTCI over the same grid. The analyses of the sensitivity of UTCI to humidity, radiation and wind speed showed plausible reactions in the heat as well as in the cold, and indicate that UTCI may in this regard be universally useable in the major areas of research and application in human biometeorology.
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| 6. |
- Leinøe, Eva, et al.
(författare)
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Application of whole-exome sequencing to direct the specific functional testing and diagnosis of rare inherited bleeding disorders in patients from the Öresund Region, Scandinavia
- 2017
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048. ; 179:2, s. 308-322
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Tidskriftsartikel (refereegranskat)abstract
- Rare inherited bleeding disorders (IBD) are a common cause of bleeding tendency. To ensure a correct diagnosis, specialized laboratory analyses are necessary. This study reports the results of an upfront diagnostic strategy using targeted whole exome sequencing. In total, 156 patients with a significant bleeding assessment tool score participated in the study, of which a third had thrombocytopenia. Eighty-seven genes specifically associated with genetic predisposition to bleeding were analysed by whole exome sequencing. Variants were classified according to the five-tier scheme. We identified 353 germline variants. Eight patients (5%) harboured a known pathogenic variant. Of the 345 previously unknown variants, computational analyses predicted 99 to be significant. Further filtration according to the Mendelian inheritance pattern, resulted in 59 variants being predicted to be clinically significant. Moreover, 34% (20/59) were assigned as novel class 4 or 5 variants upon targeted functional testing. A class 4 or 5 variant was identified in 30% of patients with thrombocytopenia (14/47) versus 11% of patients with a normal platelet count (12/109) (P < 0·01). An IBD diagnosis has a major clinical impact. The genetic investigations detailed here extricated our patients from a diagnostic conundrum, thus demonstrating that continuous optimization of the diagnostic work-up of IBD is of great benefit.
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| 7. |
- Pipe, Steven W., et al.
(författare)
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Gene Therapy with Etranacogene Dezaparvovec for Hemophilia B
- 2023
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 388:8, s. 706-718
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Tidskriftsartikel (refereegranskat)abstract
- Background: Moderate-to-severe hemophilia B is treated with lifelong, continuous coagulation factor IX replacement to prevent bleeding. Gene therapy for hemophilia B aims to establish sustained factor IX activity, thereby protecting against bleeding without burdensome factor IX replacement. Methods: In this open-label, phase 3 study, after a lead-in period (≥6 months) of factor IX prophylaxis, we administered one infusion of adeno-associated virus 5 (AAV5) vector expressing the Padua factor IX variant (etranacogene dezaparvovec; 2×1013 genome copies per kilogram of body weight) to 54 men with hemophilia B (factor IX activity ≤2% of the normal value) regardless of preexisting AAV5 neutralizing antibodies. The primary end point was the annualized bleeding rate, evaluated in a noninferiority analysis comparing the rate during months 7 through 18 after etranacogene dezaparvovec treatment with the rate during the lead-in period. Noninferiority of etranacogene dezaparvovec was defined as an upper limit of the two-sided 95% Wald confidence interval of the annualized bleeding rate ratio that was less than the noninferiority margin of 1.8. Superiority, additional efficacy measures, and safety were also assessed. Results: The annualized bleeding rate decreased from 4.19 (95% confidence interval [CI], 3.22 to 5.45) during the lead-in period to 1.51 (95% CI, 0.81 to 2.82) during months 7 through 18 after treatment, for a rate ratio of 0.36 (95% Wald CI, 0.20 to 0.64; P<0.001), demonstrating noninferiority and superiority of etranacogene dezaparvovec as compared with factor IX prophylaxis. Factor IX activity had increased from baseline by a least-squares mean of 36.2 percentage points (95% CI, 31.4 to 41.0) at 6 months and 34.3 percentage points (95% CI, 29.5 to 39.1) at 18 months after treatment, and usage of factor IX concentrate decreased by a mean of 248,825 IU per year per participant in the post-treatment period (P<0.001 for all three comparisons). Benefits and safety were observed in participants with predose AAV5 neutralizing antibody titers of less than 700. No treatment-related serious adverse events occurred. Conclusions: Etranacogene dezaparvovec gene therapy was superior to prophylactic factor IX with respect to the annualized bleeding rate, and it had a favorable safety profile.
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| 8. |
- Risum, Malene, et al.
(författare)
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Introduction of a Comprehensive Diagnostic and Interdisciplinary Management Approach in Haematological Patients with Mucormycosis : A Pre and Post-Intervention Analysis
- 2020
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Ingår i: JOURNAL OF FUNGI. - : MDPI. - 2309-608X. ; 6:4
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Tidskriftsartikel (refereegranskat)abstract
- Mucormycosis is a life threatening infection in patients with haematological disease. We introduced a Mucorales-PCR and an aggressive, multidisciplinary management approach for mucormycosis during 2016-2017 and evaluated patient outcomes in 13 patients diagnosed and treated in 2012-2019. Management principle: repeated surgical debridement until biopsies from the resection margins were clean as defined by negative Blankophor microscopy, Mucorales-PCR (both reported within 24 h), and cultures. Cultured isolates underwent EUCAST E.Def 9.3.1 susceptibility testing. Antifungal therapy (AFT) (mono/combination) combined with topical AFT (when possible) was given according to the minimal inhibitory concentration (MIC), severity of the infection, and for azoles, specifically, it was guided by therapeutic drug monitoring. The outcome was evaluated by case record review. All patients underwent surgery guided by diagnostic biopsies from tissue and resection margins (195 samples in total). Comparing 2012-2015 and 2016-2019, the median number of patients of surgical debridements was 3 and 2.5 and of diagnostic samples: microscopy/culture/PCR was 3/3/6 and 10.5/10/10.5, respectively. The sensitivity of microscopy (76%) and Mucorales-PCR (70%) were similar and microscopy was superior to that of culture (53%; p = 0.039). Initial systemic AFT was liposomal amphotericin B (n = 12) or posaconazole (n = 1) given as monotherapy (n = 4) or in combination with isavuconazole/posaconazole (n = 3/6) and terbinafine (n = 3). Nine patients received topical amphotericin B. All received isavuconazole or posaconazole consolidation therapy (n = 13). Mucormycosis related six month mortality was 3/5 in 2012-2015 and 0/7 patients in 2016-2019 (one patient was lost for follow-up). Implementation of combination therapy (systemic+topical AFT/combination systemic AFT) and aggressive surgical debridement guided by optimised diagnostic tests may improve the outcome of mucormycosis in haematologic patients.
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| 9. |
- Schjøtt, Jan, et al.
(författare)
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Use of References in Responses from Scandinavian Drug Information Centres
- 2018
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Ingår i: Medicines (Basel, Switzerland). - : MDPI. - 2305-6320. ; 5:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of this study was to compare use of references in responses from Scandinavian drug information centres (DICs). Methods: Six different fictitious drug-related queries were sent to each of seven Scandinavian DICs. The six queries concerned adverse effects, pharmacokinetics, pregnancy, complementary medicine, polypharmacy, and breast feeding. References in the responses were categorised into five types of drug information sources: primary (original studies), secondary (reviews), tertiary (drug monographs, handbooks, etc.), DIC database, or personal communication. Results: Two hundred and forty-four references were used in the 42 responses. The mean number of references varied from 3.0 to 10.6 for the six queries. The largest difference between centres with regard to number of references used (range 1?17) was found for the query on complementary medicine. In total, 124 references (50.8%) were tertiary, and only 10 of the 42 responses (23.8%) did not have any tertiary references included. Complementary medicine, breast feeding, and pregnancy were query types associated with relatively frequent use of primary references. Use of DIC database was not uncommon, but personal communications were seldom used. Conclusions: Scandinavian DICs differ substantially in number and type of references to identical drug-related queries. Tertiary sources are mainly preferred irrespective of type of query.
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