| 1. |
- Alffenaar, J. W. C., et al.
(författare)
-
Clinical standards for the dosing and management of TB drugs
- 2022
-
Ingår i: The International Journal of Tuberculosis and Lung Disease. - Paris, France : International Union Against Tuberculosis and Lung Disease. - 1027-3719 .- 1815-7920. ; 26:6, s. 483-
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Optimal drug dosing is important to ensure adequate response to treatment, prevent development of drug resistance and reduce drug toxicity. The aim of these clinical standards is to provide guidance on 'best practice' for dosing and management of TB drugs.Methods: A panel of 57 global experts in the fields of microbiology, pharmacology and TB care were identified; 51 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all participants.Results: Six clinical standards were defined: Standard 1, defining the most appropriate initial dose for TB treatment; Standard 2, identifying patients who may be at risk of sub-optimal drug exposure; Standard 3, identifying patients at risk of developing drug-related toxicity and how best to manage this risk; Standard 4, identifying patients who can benefit from therapeutic drug monitoring (TDM); Standard 5, highlighting education and counselling that should be provided to people initiating TB treatment; and Standard 6, providing essential education for healthcare professionals. In addition, consensus research priorities were identified.Conclusion: This is the first consensus-based Clinical Standards for the dosing and management of TB drugs to guide clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment to improve patient care.
|
|
| 2. |
- Singh, K. P., et al.
(författare)
-
Clinical standards for the management of adverse effects during treatment for TB
- 2023
-
Ingår i: The International Journal of Tuberculosis and Lung Disease. - : International Union Against Tuberculosis and Lung Disease. - 1027-3719 .- 1815-7920. ; 27:7, s. 506-519
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Adverse effects (AE) to TB treatment cause morbidity, mortality and treatment interruption. The aim of these clinical standards is to encourage best practise for the diagnosis and management of AE.METHODS: 65/81 invited experts participated in a Delphi process using a 5-point Likert scale to score draft standards.RESULTS: We identified eight clinical standards. Each person commencing treatment for TB should: Standard 1, be counselled regarding AE before and during treatment; Standard 2, be evaluated for factors that might increase AE risk with regular review to actively identify and manage these; Standard 3, when AE occur, carefully assessed and possible allergic or hypersensitiv-ity reactions considered; Standard 4, receive appropriate care to minimise morbidity and mortality associated with AE; Standard 5, be restarted on TB drugs after a serious AE according to a standardised protocol that includes active drug safety monitoring. In addition: Standard 6, healthcare workers should be trained on AE including how to counsel people undertaking TB treatment, as well as active AE monitoring and management; Standard 7, there should be active AE monitoring and reporting for all new TB drugs and regimens; and Standard 8, knowledge gaps identified from active AE monitoring should be systematically addressed through clinical research.CONCLUSION: These standards provide a person -centred, consensus-based approach to minimise the impact of AE TB treatment.
|
|
| 3. |
|
|
| 4. |
- Borisov, S, et al.
(författare)
-
Surveillance of adverse events in the treatment of drug-resistant tuberculosis: first global report
- 2019
-
Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 54:6
-
Tidskriftsartikel (refereegranskat)abstract
- The World Health Organization (WHO) recommends that countries implement pharmacovigilance and collect information on active drug safety monitoring (aDSM) and management of adverse events.The aim of this prospective study was to evaluate the frequency and severity of adverse events to anti-tuberculosis (TB) drugs in a cohort of consecutive TB patients treated with new (i.e. bedaquiline, delamanid) and repurposed (i.e. clofazimine, linezolid) drugs, based on the WHO aDSM project. Adverse events were collected prospectively after attribution to a specific drug together with demographic, bacteriological, radiological and clinical information at diagnosis and during therapy. This interim analysis included patients who completed or were still on treatment at time of data collection.Globally, 45 centres from 26 countries/regions reported 658 patients (68.7% male, 4.4% HIV co-infected) treated as follows: 87.7% with bedaquiline, 18.4% with delamanid (6.1% with both), 81.5% with linezolid and 32.4% with clofazimine. Overall, 504 adverse event episodes were reported: 447 (88.7%) were classified as minor (grade 1–2) and 57 (11.3%) as serious (grade 3–5). The majority of the 57 serious adverse events reported by 55 patients (51 out of 57, 89.5%) ultimately resolved. Among patients reporting serious adverse events, some drugs held responsible were discontinued: bedaquiline in 0.35% (two out of 577), delamanid in 0.8% (one out of 121), linezolid in 1.9% (10 out of 536) and clofazimine in 1.4% (three out of 213) of patients. Serious adverse events were reported in 6.9% (nine out of 131) of patients treated with amikacin, 0.4% (one out of 221) with ethionamide/prothionamide, 2.8% (15 out of 536) with linezolid and 1.8% (eight out of 498) with cycloserine/terizidone.The aDSM study provided valuable information, but implementation needs scaling-up to support patient-centred care.
|
|
| 5. |
- Forsman, Jan, et al.
(författare)
-
Density functional studies of solvation forces in hard sphere polymer solutions confined between adsorbing walls. I. Solvent effects and dependence on surface potential range.
- 2003
-
Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606. ; 118:16, s. 7672-7681
-
Tidskriftsartikel (refereegranskat)abstract
- Solvation forces between large surfaces in athermal polymer solutions, in which both solvent particles and polymers are adsorbed at the surfaces, are studied with density functional theory. We investigate how the range of the surface potential affects the net interaction between the surfaces. Predictions from treatments in which the solvent is explicitly induced are compared with those obtained with more approximate models, where the solvent is either neglected, or enters the description implicitly. The results are interpreted via comparisons with simpler model systems. It is shown that a long-ranged surface potential, acting equally on monomers and solvent, leads to a solvent dominated repulsive solvation force, while polymer specific contributions dominate the net interactions when the adsorption potential has a short range. Effects of preferential polymer adsorption are also investigated. ©2003 American Institute of Physics.
|
|
| 6. |
- Forsman, L. Davies, et al.
(författare)
-
Intra- and Extracellular Activities of Trimethoprim-Sulfamethoxazole against Susceptible and Multidrug-Resistant Mycobacterium tuberculosis
- 2014
-
Ingår i: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 58:12, s. 7557-7559
-
Tidskriftsartikel (refereegranskat)abstract
- We investigated the activity of trimethoprim-sulfamethoxazole (SXT) against Mycobacterium tuberculosis, the pathogen that causes tuberculosis (TB). The MIC distribution of SXT was 0.125/2.4 to 2/38 mg/liter for the 100 isolates tested, including multi- and extensively drug-resistant isolates (MDR/XDR-TB), whereas the intracellular MIC90 of sulfamethoxazole (SMX) for the pansusceptible strain H37Rv was 76 mg/liter. In an exploratory analysis using a ratio of the unbound area under the concentration-time curve from 0 to 24 h over MIC (fAUC(0-24)/MIC) using >= 25 as a potential target, the cumulative fraction response was >= 90% at doses of >= 2,400 mg of SMX. SXT is a potential treatment option for MDR/XDR-TB.
|
|
| 7. |
|
|
| 8. |
- Hoiseth, G., et al.
(författare)
-
Evaluating the hip-flask defence using analytical data from ethanol and ethyl glucuronide. A comparison of two models
- 2020
-
Ingår i: Forensic Science International. - : ELSEVIER IRELAND LTD. - 0379-0738 .- 1872-6283. ; 316
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: Claimed intake of alcohol after a traffic incident, called the hip-flask defence, can be objectively assessed by different methods. One of them is the use of two consecutive ethanol concentrations in urine and the ratio between ethanol concentrations in urine and blood. Another one is the concentrations of ethyl glucuronide (EtG) and ethyl sulphate (EtS) in blood and their ratio to ethanol. The experimental basis for both these models is from single dose studies only. The aim of this study was therefore to describe the kinetics of ethanol, EtG and EtS after ingestion of two repeated doses of ethanol and to investigate the usefulness of the different models for the assessment of the hip-flask defence. Methods: Thirty-five subjects ingested a first dose of 0.51 g of ethanol per kilo body weight, and two hours later a second dose (the hip-flask drink) of 0.25, 0.51 or 0.85 g of ethanol per kilo body weight. Ten urine and 17 blood samples were collected and analysed for ethanol, EtG and EtS using fully validated methods. It was investigated if all subjects fulfilled the criteria for recent drinking, according to the two different models, when using the samples collected 180-240 minutes after start of first dose drinking. According to the first model, increase in urinary ethanol concentrations and a ratio UAC/BAC below 1.3 indicated recent drinking. According to the second model, increase in blood EtG concentrations and a ratio ethanol (g/kg)/EtG (mg/L) above 1 indicated recent drinking. Results: All subjects in the high dose group fulfilled all criteria for recent drinking. One subject in the medium dose group and nine subjects in the low dose group failed to show increasing UAC and/or a UAC/ BAC ratio below 1.3. One subject in the low dose group failed to show increasing concentrations of blood EtG, but all subjects showed a ratio ethanol/EtG above 1. Conclusions: The present study showed, by the use of experimental data, that both two models used to investigate the hip-flask defence can be used, but only when the hip-flask dose is sufficiently high. (C) 2020 The Author(s). Published by Elsevier B.V.
|
|
| 9. |
|
|
| 10. |
- Laaksonen, T., et al.
(författare)
-
Sympatric divergence and clinal variation in multiple coloration traits of Ficedula flycatchers
- 2015
-
Ingår i: Journal of Evolutionary Biology. - : Wiley. - 1010-061X .- 1420-9101. ; 28:4, s. 779-790
-
Tidskriftsartikel (refereegranskat)abstract
- Geographic variation in phenotypes plays a key role in fundamental evolutionary processes such as local adaptation, population differentiation and speciation, but the selective forces behind it are rarely known. We found support for the hypothesis that geographic variation in plumage traits of the pied flycatcher Ficedula hypoleuca is explained by character displacement with the collared flycatcher Ficedula albicollis in the contact zone. The plumage traits of the pied flycatcher differed strongly from the more conspicuous collared flycatcher in a sympatric area but increased in conspicuousness with increasing distance to there. Phenotypic differentiation (P-ST) was higher than that in neutral genetic markers (F-ST), and the effect of geographic distance remained when statistically controlling for neutral genetic differentiation. This suggests that a cline created by character displacement and gene flow explains phenotypic variation across the distribution of this species. The different plumage traits of the pied flycatcher are strongly to moderately correlated, indicating that they evolve non-independently from each other. The flycatchers provide an example of plumage patterns diverging in two species that differ in several aspects of appearance. The divergence in sympatry and convergence in allopatry in these birds provide a possibility to study the evolutionary mechanisms behind the highly divergent avian plumage patterns.
|
|
