| 1. |
- Saulo, Eleonor C., et al.
(author)
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Willingness and ability to pay for artemisinin-based combination therapy in rural Tanzania
- 2008
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In: Malaria Journal. - London : BioMed Central. - 1475-2875. ; 7, s. 227-
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Journal article (peer-reviewed)abstract
- The aim of this study was to analyse willingness to pay (WTP) and ability to pay (ATP) for ACT for children below five years of age in a rural setting in Tanzania before the introduction of artemisinin-based combination therapy (ACT) as first-line treatment for uncomplicated malaria. Socio-economic factors associated with WTP and expectations on anti-malaria drugs, including ACT, were also explored.MethodsStructured interviews and focus group discussions were held with mothers, household heads, health-care workers and village leaders in Ishozi, Gera and Ishunju wards in north-west Tanzania in 2004. Contingent valuation method (CVM) was used with "take-it-or-leave-it" as the eliciting method, expressed as WTP for a full course of ACT for a child and households' opportunity cost of ACT was used to assess ATP. The study included descriptive analyses with multivariate adjustment for potential confounding factors.ResultsAmong 265 mothers and household heads, 244 (92%, CI = 88%–95%) were willing to pay Tanzanian Shillings (TSh) 500 (US$ 0.46) for a child's dose of ACT, but only 55% (49%–61%) were willing to pay more than TSh 500. Mothers were more often willing to pay than male household heads (adjusted odds ratio = 2.1, CI = 1.2–3.6). Socio-economic status had no significant effect on WTP. The median annual non-subsidized ACT cost for clinical malaria episodes in an average household was calculated as US$ 6.0, which would represent 0.9% of the average total consumption expenditures as estimated from official data in 2001. The cost of non-subsidized ACT represented 7.0% of reported total annual expenditure on food and 33.0% of total annual expenditure on health care."Rapid effect," "no adverse effect" and "inexpensive" were the most desired features of an anti-malarial drug.ConclusionWTP for ACT in this study was less than its real cost and a subsidy is, therefore, needed to enable its equitable affordability. The decision taken in Tanzania to subsidize Coartem® fully at governmental health care facilities and at a consumer price of TSh 300–500 (US$ 0.28–0.46) at special designated shops through the programme of Accredited Drug Dispensing Outlets (ADDOs) appears to be well founded.
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| 2. |
- Svedbo Engström, Maria, 1980, et al.
(author)
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A disease-specific questionnaire for measuring patient-reported outcomes and experiences in the Swedish National Diabetes Register: Development and evaluation of content validity, face validity, and test-retest reliability
- 2018
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In: Patient Education and Counseling. - : Elsevier BV. - 0738-3991 .- 1873-5134. ; 101:1, s. 139-146
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Journal article (peer-reviewed)abstract
- Objective: To describe the development and evaluation of the content and face validity and test-retest reliability of a disease-specific questionnaire that measures patient-reported outcomes and experiences for the Swedish National Diabetes Register for adult patients who have type 1 or type 2 diabetes. Methods: In this methodological study, a questionnaire was developed over four phases using an iterative process. Expert reviews and cognitive interviews were conducted to evaluate content and face validity, and a postal survey was administered to evaluate test-retest reliability. Results: The expert reviews and cognitive interviews found the disease-specific questionnaire to be understandable, with relevant content and value for diabetes care. An item-level content validity index ranged from 0.6-1.0 and a scale content validity/average ranged from 0.7-1.0. The fourth version, with 33 items, two main parts and seven dimensions, was answered by 972 adults with type 1 and type 2 diabetes (response rate 61%). Weighted Kappa values ranged from 0.31-0.78 for type 1 diabetes and 0.27-0.74 for type 2 diabetes. Conclusions: This study describes the initial development of a disease-specific questionnaire in conjunction with the NDR. Content and face validity were confirmed and test-retest reliability was satisfactory. Practice implications: With the development of this questionnaire, the NDR becomes a clinical tool that contributes to further understanding the perspectives of adult individuals with diabetes. (c) 2017 Elsevier B.V. All rights reserved.
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| 3. |
- Di Gennaro, A., et al.
(author)
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Cysteinyl leukotriene receptor 1 antagonism prevents experimental abdominal aortic aneurysm
- 2018
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 115:8, s. 1907-1912
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Journal article (peer-reviewed)abstract
- Cysteinyl-leukotrienes (cys-LTs) are 5-lipoxygenase-derived lipid mediators involved in the pathogenesis and progression of inflammatory disorders, in particular asthma. We have previously found evidence linking these mediators to increased levels of proteolytic enzymes in tissue specimens of human abdominal aortic aneurysm (AAA). Here we show that antagonism of the CysLT1 receptor by montelukast, an established antiasthma drug, protects against a strong aorta dilatation (>50% increase = aneurysm) in a mouse model of CaCl2-induced AAA at a dose comparable to human medical practice. Analysis of tissue extracts revealed that montelukast reduces the levels of matrix metalloproteinase-9 (MMP-9) and macrophage inflammatory protein-1 alpha (MIP-1 alpha) in the aortic wall. Furthermore, aneurysm progression was specifically mediated through CysLT1 signaling since a selective CysLT2 antagonist was without effect. A significantly reduced vessel dilatation is also observed when treatment with montelukast is started days after aneurysm induction, suggesting that the drug not only prevents but also stops and possibly reverts an already ongoing degenerative process. Moreover, montelukast reduced the incidence of aortic rupture and attenuated the AAA development in two additional independent models, i.e., angiotensin II- and porcine pancreatic elastase-induced AAA, respectively. Our results indicate that cys-LTs are involved in the pathogenesis of AAA and that antagonism of the CysLT1 receptor is a promising strategy for preventive and therapeutic treatment of this clinically silent and highly lethal disease.
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| 4. |
- Nijsingh, Niels, 1977, et al.
(author)
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Managing pollution from antibiotics manufacturing: charting actors, incentives and disincentives
- 2019
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In: Environmental health. - : Springer Science and Business Media LLC. - 1476-069X. ; 18
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Journal article (peer-reviewed)abstract
- Background Emissions of high concentrations of antibiotics from manufacturing sites select for resistant bacteria and may contribute to the emergence of new forms of resistance in pathogens. Many scientists, industry, policy makers and other stakeholders recognize such pollution as an unnecessary and unacceptable risk to global public health. An attempt to assess and reduce such discharges, however, quickly meets with complex realities that need to be understood to identify effective ways to move forward. This paper charts relevant key actor-types, their main stakes and interests, incentives that can motivate them to act to improve the situation, as well as disincentives that may undermine such motivation. Methods The actor types and their respective interests have been identified using research literature, publicly available documents, websites, and the knowledge of the authors. Results Thirty-three different actor-types were identified, representing e.g. commercial actors, public agencies, states and international institutions. These are in complex ways connected by interests that sometimes may conflict and sometimes pull in the same direction. Some actor types can act to create incentives and disincentives for others in this area. Conclusions The analysis demonstrates and clarifies the challenges in addressing industrial emissions of antibiotics, notably the complexity of the relations between different types of actors, their international dependency and the need for transparency. The analysis however also suggests possible ways of initiating incentive-chains to eventually improve the prospects of motivating industry to reduce emissions. High-resource consumer states, especially in multinational cooperation, hold a key position to initiate such chains.
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| 5. |
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| 6. |
- Sjölander, Maria, 1970-
(author)
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Use of secondary preventive drugs after stroke
- 2013
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Doctoral thesis (other academic/artistic)abstract
- Background Stroke is a serious condition that can have significant impact on an individual’s health and is a significant burden on public health and public finances. Secondary preventive drug treatment after stroke is important for decreasing the risk of recurrent strokes. Non-adherence to drug treatment hampers the treatment effect, especially in long-term preventive treatments. The aim of this thesis was to study the use of secondary preventive drugs after stroke among Swedish stroke patients in terms of inequalities in implementation in clinical practice and patient adherence to treatment over time.Methods Riks-Stroke, the Swedish stroke register, was used to sample stroke patients and as a source of information on background characteristics and medical and health care-related information including information on prescribed preventive drugs. The patients that were included had a stroke between 2004 and 2012. Individual patient data on prescriptions filled in Swedish pharmacies were retrieved from the Swedish Prescribed Drug Register and used to estimate patient adherence to drug treatment. Data on education, income, and country of birth were included from the LISA database at Statistics Sweden. A questionnaire survey was used to collect information about patients’ perceptions about stroke, beliefs about medicines, and self-reported adherence.Results Results showed that a larger proportion of men than women were prescribed statins and warfarin after stroke. There was also a social stratification in the prescribing of statins. Patients with higher income and a higher level of education were more likely to be prescribed a statin compared to patients with low income and low level of education. Statins were also more often prescribed to patients born in Nordic countries, Europe, or outside of Europe compared to patients born in Sweden. Primary non-adherence (not continuing treatment at all within 4 months of discharge from hospital) was low for preventive drug treatment after stroke. Data on filled prescriptions, however, indicated that the proportion of patients who continued to use the drugs declined during the first 2 years after stroke. For most drugs, refill adherence in drug treatment was associated with female sex, good self-rated health, and living in institutions and (for antihypertensive drugs and statins) having used the drug before the stroke. For statins and warfarin, a first-ever stroke was also associated with continuous drug use. Self-reported adherence 3 months after stroke also showed associations with patients’ personal beliefs about medicines; non-adherent patients scored higher on negative beliefs and lower on positive beliefs about medicines.Conclusion Inequalities between men and women and between different socioeconomic groups were found in the prescribing of secondary preventive drugs after stroke. Only a small proportion of Swedish stroke patients did not continue treatment after discharge from hospital, but the proportion of non-adherent patients increased over time. Poor adherence to preventive drug treatment after stroke is a public health problem, and improving adherence to drug treatment requires consideration of patients’ personal beliefs and perceptions about drugs.
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| 7. |
- Forslund, Sofia K., et al.
(author)
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Combinatorial, additive and dose-dependent drug–microbiome associations
- 2021
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 600:7889, s. 500-505
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Journal article (peer-reviewed)abstract
- During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery1–5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug–host–microbiome interactions in cardiometabolic disease.
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| 8. |
- Turanli, Beste, et al.
(author)
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Drug Repositioning for Effective Prostate Cancer Treatment
- 2018
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In: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 9
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Journal article (peer-reviewed)abstract
- Drug repositioning has gained attention from both academia and pharmaceutical companies as an auxiliary process to conventional drug discovery. Chemotherapeutic agents have notorious adverse effects that drastically reduce the life quality of cancer patients so drug repositioning is a promising strategy to identify non-cancer drugs which have anti-cancer activity as well as tolerable adverse effects for human health. There are various strategies for discovery and validation of repurposed drugs. In this review, 25 repurposed drug candidates are presented as result of different strategies, 15 of which are already under clinical investigation for treatment of prostate cancer (PCa). To date, zoledronic acid is the only repurposed, clinically used, and approved non-cancer drug for PCa. Anti-cancer activities of existing drugs presented in this review cover diverse and also known mechanisms such as inhibition of mTOR and VEGFR2 signaling, inhibition of PI3K/Akt signaling, COX and selective COX-2 inhibition, NF-kappa B inhibition, Wnt/beta - Catenin pathway inhibition, DNMT1 inhibition, and GSK-3 beta inhibition. In addition to monotherapy option, combination therapy with current anti-cancer drugs may also increase drug efficacy and reduce adverse effects. Thus, drug repositioning may become a key approach for drug discovery in terms of time- and cost-efficiency comparing to conventional drug discovery and development process.
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| 9. |
- Malmqvist, Erik, et al.
(author)
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Pharmaceutical Pollution from Human use and the Polluter Pays Principle
- 2023
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In: Public Health Ethics. - 1754-9973 .- 1754-9981. ; 16:2, s. 152-164
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Journal article (peer-reviewed)abstract
- Human consumption of pharmaceuticals often leads to environmental release of residues via urine and faeces, creating environmental and public health risks. Policy responses must consider the normative question how responsibilities for managing such risks, and costs and burdens associated with that management, should be distributed between actors. Recently, the Polluter Pays Principle (PPP) has been advanced as rationale for such distribution. While recognizing some advantages of PPP, we highlight important ethical and practical limitations with applying it in this context: PPP gives ambiguous and arbitrary guidance due to difficulties in identifying the salient polluter. Moreover, when PPP does identify responsible actors, these may be unable to avoid or mitigate their contribution to the pollution, only able to avoid/mitigate it at excessive cost to themselves or others, or excusably ignorant of contributing. These limitations motivate a hybrid framework where PPP, which emphasizes holding those causing large-scale problems accountable, is balanced by the Ability to Pay Principle (APP), which emphasizes efficiently managing such problems. In this framework, improving wastewater treatment and distributing associated financial costs across water consumers or taxpayers stand out as promising responses to pharmaceutical pollution from human use. However, sound policy depends on empirical considerations requiring further study.
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| 10. |
- Altay, Özlem, et al.
(author)
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Current Status of COVID-19 Therapies and Drug Repositioning Applications
- 2020
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In: Iscience. - : Elsevier BV. - 2589-0042. ; 23:7
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Journal article (peer-reviewed)abstract
- The rapid and global spread of a new human coronavirus (SARS-CoV-2) has produced an immediate urgency to discover promising targets for the treatment of COVID-19. Drug repositioning is an attractive approach that can facilitate the drug discovery process by repurposing existing pharmaceuticals to treat illnesses other than their primary indications. Here, we review current information concerning the global health issue of COVID-19 including promising approved drugs and ongoing clinical trials for prospective treatment options. In addition, we describe computational approaches to be used in drug repurposing and highlight examples of in silico studies of drug development efforts against SARS-CoV-2.
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