Browsing by Subject "Therapy"

Now showing 1 - 6 of 6
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    Efficacy of budesonide/formoterol maintenance and reliever therapy compared with higher-dose budesonide as step-up from low-dose inhaled corticosteroid treatment
    (2017) Jenkins, Christine R; Eriksson, Göran; Bateman, Eric D; Reddel, Helen K; Sears, Malcolm R; Lindberg, Magnus; O’Byrne, Paul M
    Asthma management may involve a step up in treatment when symptoms are not well controlled. We examined whether budesonide/formoterol maintenance and reliever therapy (MRT) is as effective as higher, fixed-dose budesonide plus as-needed terbutaline in patients requiring step-up from Step 2 treatment (low-dose inhaled corticosteroids), stratified by baseline reliever use.
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    Hyaline membrane disease: a study of lung function and treatment
    (1967) Harrison, V C
    At present, both the aetiology of hyaline membrane disease and a means of preventing it remain unknown. Recent studies indicate that a significant number of infants die of respiratory failure but there is no general agreement concerning the changes of pulmonary function which lead to this stage. Two approaches have been used in the treatment of respiratory decompensation. First it has been proposed that blood gas and acid base abnormalities which result from respiratory failure can be prevented by oxygen and intravenous alkali and secondly an attempt has been made to correct abnormal lung function itself by means of artificial ventilation. These methods are directed at different aspects of the problem and their efficacy is as yet not established. The application of artificial ventilation in particular must depend on the nature of any ventilation, diffusion or perfusion defect.
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    Nonlinear mixed-effects modelling of drug-drug interactions between antiretroviral therapy and tuberculosis treatment
    (2025) Kengo, Allan; Denti, Paolo; Resendiz Galvan, Juan Eduardo
    Human immunodeficiency virus (HIV) remains a significant global health challenge that affected approximately 39 million individuals in 2022, with majority residing in Africa. Among people with HIV (PWH), co-infection with tuberculosis (TB) is a leading cause of death. However, the concurrent treatment of HIV and TB often results in drug-drug interactions (DDIs), mediated especially by rifampicin, a key component of the TB regimen and potent enzyme and transporter inducer. These DDIs may compromise treatment safety and efficacy, potentially leading to therapeutic failure and increased risk of drug resistance. In this thesis, we utilized non-linear mixed effects modelling and data from studies in PWH and healthy volunteers to characterize DDIs between first- and second-line antiretroviral (ARV) and anti-TB drugs. Additionally, we performed simulations to assess treatment target attainment following current dosing recommendations in PWH. Our pharmacokinetic model of standard- and high-dose rifampicin in PWH identified lower bioavailability of the top-up capsule formulation as the cause of lower-than-expected drug exposures in participants on high-dose rifampicin. Furthermore, the reduced dolutegravir exposures in participants on concurrent high-dose rifampicin, compared to those on the standard-dose, were attributed to reduced bioavailability rather than enhanced clearance. Notably, our simulations demonstrated that doubling the dosing frequency of dolutegravir effectively counteracted the DDI with both standard- and high-dose rifampicin. Secondly, we characterized the DDI between ritonavir-boosted atazanavir (ATV/r) and rifampicin, both in plasma and within peripheral blood mononuclear cells (PBMCs). Rifampicin increased the clearance of ATV/r by threefold, and doubling the dosing frequency of ATV/r was sufficient to counteract this interaction and restore treatment target attainment. Notably, rifampicin did not affect atazanavir equilibration or accumulation in PBMCs, suggesting that plasma studies can reliably reflect intracellular processes. We also applied our model to an external dataset, estimating a twofold decrease in atazanavir clearance, likely due to ritonavir co-administration. Lastly, we found clofazimine, a second-line drug resistant TB (DR-TB) drug, to increase the clearance of levofloxacin by 15% but not affect the pharmacokinetics of cycloserine, linezolid, or isoniazid. This confirmed that clofazimine can be safely co-administered with other DR-TB drugs, as it poses minimal risk of significant DDIs. In conclusion, non-linear mixed effects modelling can be used to evaluate DDIs, and we recommend its incorporation in routine dose optimization and therapeutic drug monitoring programs to enhance treatment outcomes.
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    The immunological response to syphilis differs by HIV status; a prospective observational cohort study
    (2017) Kenyon, Chris; Osbak, Kara Krista; Crucitti, Tania; Kestens, Luc
    BACKGROUND: It is not known if there is a difference in the immune response to syphilis between HIV-infected and uninfected individuals. METHODS: We prospectively recruited all patients with a new diagnosis of syphilis and tested their plasma for IFNα, IFNγ, IL-1β, IL-12p40, IL-12p70, IP-10, MCP-1, MIP-1α, MIP-1β, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10 and IL-17A at baseline pre-treatment and 6 months following therapy. RESULTS: A total of 79 HIV-infected [44 primary/secondary syphilis (PSS) and 35 latent syphilis (LS)] and 12 HIV-uninfected (10 PSS and 2 LS) cases of syphilis and 30 HIV-infected controls were included in the study. At the baseline visit, compared to the control group, concentrations of IL-10 were significantly elevated in the HIV-infected and uninfected groups. The level of IL-10 was significantly higher in the HIV-infected compared to the HIV-uninfected PSS group (25.3 pg/mL (IQR, 4.56-41.76) vs 2.73 pg/mL (IQR, 1.55-9.02), P = 0.0192). In the HIV-infected PSS group (but not the HIV-infected LS or HIV-uninfected PSS groups) the IP-10, MIP-1b, IL-6 and IL-8 were raised compared to the controls. IL-10 levels decreased but did not return to control baseline values by 6 months in HIV infected PSS and LS and HIV uninfected PSS. CONCLUSION: PSS and LS in HIV-infected individuals is characterized by an increase in inflammatory and anti-inflammatory cytokines such as IL-10. The increase of IL-10 is greater in HIV-infected than uninfected individuals. Further work is required to ascertain if this is part of an immunological profile that correlates with adverse outcomes such as serofast syphilis and neurosyphilis, in HIV-infected individuals.
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    The international WAO/EAACI guideline for the management of hereditary angioedema – the 2017 revision and update
    (BioMed Central, 2018-02-27) Maurer, Marcus; Magerl, Markus; Ansotegui, Ignacio; Aygören-Pürsün, Emel; Betschel, Stephen; Bork, Konrad; Bowen, Tom; Boysen, Henrik B; Farkas, Henriette; Grumach, Anete S; Hide, Michihiro; Katelaris, Constance; Lockey, Richard; Longhurst, Hilary; Lumry, William R.; Martinez-Saguer, Inmaculada; Moldovan, Dumitru; Nast, Alexander; Pawankar, Ruby; Potter, Paul; Riedl, Marc; Ritchie, Bruce; Rosenwasser, Lanny; Sánchez-Borges, Mario; Zhi, Yuxiang; Zuraw, Bruce; Craig, Timothy
    Hereditary Angioedema (HAE) is a rare and disabling disease. Early diagnosis and appropriate therapy are essential. This update and revision of the global guideline for HAE provides up-to-date consensus recommendations for the management of HAE. In the development of this update and revision of the guideline, an international expert panel reviewed the existing evidence and developed 20 recommendations that were discussed, finalized and consented during the guideline consensus conference in June 2016 in Vienna. The final version of this update and revision of the guideline incorporates the contributions of a board of expert reviewers and the endorsing societies. The goal of this guideline update and revision is to provide clinicians and their patients with guidance that will assist them in making rational decisions in the management of HAE with deficient C1-inhibitor (type 1) and HAE with dysfunctional C1-inhibitor (type 2). The key clinical questions covered by these recommendations are: 1) How should HAE-1/2 be defined and classified?, 2) How should HAE-1/2 be diagnosed?, 3) Should HAE-1/2 patients receive prophylactic and/or on-demand treatment and what treatment options should be used?, 4) Should HAE-1/2 management be different for special HAE-1/2 patient groups such as pregnant/lactating women or children?, and 5) Should HAE-1/2 management incorporate self-administration of therapies and patient support measures? This article is co-published with permission in Allergy and the World Allergy Organization Journal.
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    The Ngoma Consciousness: IsiNgqi neSandi as existing and accessible tools for healing and therapy in Africa
    (2025) Koela, Nkosenathi; Ramugondo, Elelwani; Pather, Jayendran; Bam-Hutchison, June
    This thesis explores the ritual archive of isingqi (energy, rhythm and vibration) used in Ngoma (the divination arts and ecology) through ingoma (traditional sound and chants) as accessible tools for healing and therapy. Ngoma, etymologically, is a proto-Bantu term for an African praxis within which exists an ecology of related institutions such as the practice of medicine, divination, crafts, music, and ritual. Central in this thesis is the systemic dispossession and destruction of indigene ecologies of healing in South Africa as a result of coloniality, which De Sousa Santos (2015) unpacks through the framework of epistimicide and I unpack through the framework of ecolocide and musicolocide. The central question this thesis seeks to answer is: How is ritual involving isingqi used and preserved in the divination arts of/through ingoma (traditional sound and chants)? The overall objective is to unpack and explore this African (Ngoma) philosophical praxis and its related ecology of knowledge, through the applied method of ritual music as vibrations of healing in Southern Africa, and to offer an informed and decolonial use of ritual technologies such as ingoma and isingqi. To do this, I draw from inter-disciplinary research and archival literature that explores various epistemologies and uses of sound in African indigene communities. I also use the existing ritual archive of Ngoma and its modalities through a co-operative co-design method. The practical elements of my research provide a repository within which to explore some of the possibilities of Ngoma as consciousness, an ecology of divination arts, and praxis in the current context. This thesis argues that African indigenous scholars must engage deeply with African epistemologies like Ngoma to develop authentic technologies and healing modalities that can enrich South Africa's cultural and healing ecology. Doing so may help reinstate African- conscious institutions of healing in various sectors of society and introduce hybrid forms of sound therapy and psychosomatic treatments, involving unique healing methods through Ngoma rhythmic manipulation. My findings argue for a clear distinction between performance studies and indigene ritual studies. This distinction can provide a platform for interdisciplinary models of scholarship that enrich indigene knowledge systems and encourage research into African healing praxes.