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1.
  • Mohammadi, Elyas, et al. (författare)
  • Applications of Genome-Wide Screening and Systems Biology Approaches in Drug Repositioning
  • 2020
  • Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:9, s. 1-24
  • Forskningsöversikt (refereegranskat)abstract
    • Simple Summary Drug repurposing is an accelerated route for drug development and a promising approach for finding medications for orphan and common diseases. Here, we compiled databases that comprise both computationally- or experimentally-derived data, and categorized them based on quiddity and origin of data, further focusing on those that present high throughput omic data or drug screens. These databases were then contextualized with genome-wide screening methods such as CRISPR/Cas9 and RNA interference, as well as state of art systems biology approaches that enable systematic characterizations of multi-omic data to find new indications for approved drugs or those that reached the latest phases of clinical trials. Modern drug discovery through de novo drug discovery entails high financial costs, low success rates, and lengthy trial periods. Drug repositioning presents a suitable approach for overcoming these issues by re-evaluating biological targets and modes of action of approved drugs. Coupling high-throughput technologies with genome-wide essentiality screens, network analysis, genome-scale metabolic modeling, and machine learning techniques enables the proposal of new drug-target signatures and uncovers unanticipated modes of action for available drugs. Here, we discuss the current issues associated with drug repositioning in light of curated high-throughput multi-omic databases, genome-wide screening technologies, and their application in systems biology/medicine approaches.
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2.
  • Di Gennaro, A., et al. (författare)
  • Cysteinyl leukotriene receptor 1 antagonism prevents experimental abdominal aortic aneurysm
  • 2018
  • Ingår i: 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
  • Tidskriftsartikel (refereegranskat)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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3.
  • Turanli, Beste, et al. (författare)
  • Drug Repositioning for Effective Prostate Cancer Treatment
  • 2018
  • Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 9
  • Tidskriftsartikel (refereegranskat)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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5.
  • Altay, Özlem, et al. (författare)
  • Current Status of COVID-19 Therapies and Drug Repositioning Applications
  • 2020
  • Ingår i: Iscience. - : Elsevier BV. - 2589-0042. ; 23:7
  • Tidskriftsartikel (refereegranskat)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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6.
  • Xin, D. L., et al. (författare)
  • Effectiveness of conservative interventions for sickness and pain behaviors induced by a high repetition high force upper extremity task
  • 2017
  • Ingår i: BMC Neuroscience. - : BioMed Central. - 1471-2202. ; 18
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Systemic inflammation is known to induce sickness behaviors, including decreased social interaction and pain. We have reported increased serum inflammatory cytokines in a rat model of repetitive strain injury (rats perform an upper extremity reaching task for prolonged periods). Here, we sought to determine if sickness behaviors are induced in this model and the effectiveness of conservative treatments.Methods: Experimental rats underwent initial training to learn a high force reaching task (10 min/day, 5 days/week for 6 weeks), with or without ibuprofen treatment (TRHF vs. TRHF + IBU rats). Subsets of trained animals went on to perform a high repetition high force (HRHF) task for 6 or 12 weeks (2 h/day, 3 days/week) without treatment, or received two secondary interventions: ibuprofen (HRHF + IBU) or a move to a lower demand low repetition low force task (HRHF-to-LRLF), beginning in task week 5. Mixed-effects models with repeated measures assays were used to assay duration of social interaction, aggression, forepaw withdrawal thresholds and reach performance abilities. One-way and two-way ANOVAs were used to assay tissue responses. Corrections for multiple comparisons were made.Results: TRHF + IBU rats did not develop behavioral declines or systemic increases in IL-1beta and IL-6, observed in untreated TRHF rats. Untreated HRHF rats showed social interaction declines, difficulties performing the operant task and forepaw mechanical allodynia. Untreated HRHF rats also had increased serum levels of several inflammatory cytokines and chemokines, neuroinflammatory responses (e.g., increased TNFalpha) in the brain, median nerve and spinal cord, and Substance P and neurokinin 1 immunoexpression in the spinal cord. HRHF + IBU and HRHF-to-LRLF rats showed improved social interaction and reduced inflammatory serum, nerve and brain changes. However, neither secondary treatment rescued HRHF-task induced forepaw allodynia, or completely attenuated task performance declines or spinal cord responses.Conclusions: These results suggest that inflammatory mechanisms induced by prolonged performance of high physical demand tasks mediate the development of social interaction declines and aggression. However, persistent spinal cord sensitization was associated with persistent behavioral indices of discomfort, despite use of conservative secondary interventions indicating the need for prevention or more effective interventions.
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7.
  • Cappelletto, Elia, et al. (författare)
  • Impact of Post Manufacturing Handling of Protein-Based Biologic Drugs on Product Quality and User Centricity
  • 2024
  • Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier. - 0022-3549 .- 1520-6017.
  • Tidskriftsartikel (refereegranskat)abstract
    • This article evaluates the current gaps around the impact of post-manufacturing processes on the product qualities of protein-based biologics, with a focus on user centricity. It includes the evaluation of the regulatory guidance available, describes a collection of scientific literature and case studies to showcase the impact of post-manufacturing stresses on product and dosing solution quality. It also outlines the complexity of clinical handling and the need for communication, and alignment between drug providers, healthcare professionals, users, and patients. Regulatory agencies provide clear expectations for drug manufacturing processes, however, guidance supporting post-product manufacturing handling is less defined and often misaligned. This is problematic as the pharmaceutical products experience numerous stresses and processes which can potentially impact drug quality, safety and efficacy. This article aims to stimulate discussion amongst pharmaceutical developers, health care providers, device manufacturers, and public researchers to improve these processes. Patients and caregivers' awareness can be achieved by providing relevant educational material on pharmaceutical product handling.
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8.
  • Bondesson, Åsa ÅB, et al. (författare)
  • A structured questionnaire to assess patient compliance and beliefs about medicines taking into account the ordered categorical structure of data
  • 2009
  • Ingår i: Journal of Evaluation In Clinical Practice. - : Wiley. - 1356-1294 .- 1365-2753. ; 15:4, s. 713-723
  • Tidskriftsartikel (refereegranskat)abstract
    • RATIONALE, AIMS AND OBJECTIVE: The objectives were to describe and evaluate the structured medication questionnaire and to improve data handling of results from the Morisky four-item scale for patient compliance and Beliefs about Medicines Questionnaire-specific (BMQ-specific). METHODS: A questionnaire was developed with the purpose of being used when identifying medication errors and assessing patient compliance to and beliefs about medicines. RESULTS: A majority of the respondents (62%; CI 45-77%) had at least one medication error. Assuming that all items are equally important in the Morisky four-item scale we presented four alternative ways to create a unidimensional global scale. A two-dimensional global scale was also constructed. The results from the BMQ-specific were presented in different ways, all taking into account that the scale has ordered verbal categories: at the level addressing each specific question, at the sub-scales 'concern' and 'necessity' level and at the global level. CONCLUSIONS: The structured medication questionnaire can be used in daily practice as a tool to identify drug-related problems. The choice of how to use and present data from those scales in research depends on patient characteristics and how discriminating one would like the scales to be.
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9.
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10.
  • Salomé, Nicolas, et al. (författare)
  • Anorexigenic and electrophysiological actions of novel ghrelin receptor (GHS-R1A) antagonists in rats
  • 2009
  • Ingår i: European Journal of Pharmacology. - : Elsevier. - 0014-2999 .- 1879-0712. ; 612:1-3, s. 167-173
  • Tidskriftsartikel (refereegranskat)abstract
    • Here we provide the first pharmacological exploration of the impact of acute central nervous system exposure to three recently developed ghrelin receptor (GHS-R1A) ligands on food intake and on the electrical activity of the target cells for ghrelin in the hypothalamus. Central (i.c.v) injection of GHS-R1A antagonists to rats suppressed food intake induced by i.c.v ghrelin injection (1 mu g) in a dose-dependent manner with a total blockade at concentraions of 0.4 mu g and 8 mu g for JMV 3002 and JMV 2959 respectively. JMV 2810, a partial agonist, also suppressed ghrelin-induced food intake (range: 0.02-2 mu g). Moreover all three compounds reduced fasting-induced food intake in rats (i.e. the amount of food eaten during the first hour of food exposure after a 16 h fast). At the single cell level we also explored the effects of the compounds to suppress ghrelin (0.5 mu M)-induced changes in electrical activity of arcuate nucleus cells recorded extracellularly in a slice preparation. Preincubation followed by perfusion with the GHS-R1A ligands suppressed the responsiveness of arcuate cells to ghrelin. Thus, the recently developed GHS-R1A ligands (JMV 3002, 2959 and 2810) suppress ghrelin-induced and fasting-induced food intake at the level of the central nervous system. This appears to be mediated, at least in part, by a modulation of the activity of ghrelin-responsive arcuate nucleus cells. As the central ghrelin signalling system has emerged as an important pro-obesity target, it will be important to establish the efficacy of these GHS-R1A ligands to reduce fast mass in clincal studies.
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11.
  • Ekqvist, David, et al. (författare)
  • Safety and pharmacokinetics-pharmacodynamics of a shorter tuberculosis treatment with high-dose pyrazinamide and rifampicin : a study protocol of a phase II clinical trial (HighShort-RP)
  • 2022
  • Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 12:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Increased dosing of rifampicin and pyrazinamide seems a viable strategy to shorten treatment and prevent relapse of drug-susceptible tuberculosis (TB), but safety and efficacy remains to be confirmed. This clinical trial aims to explore safety and pharmacokinetics-pharmacodynamics of a high-dose pyrazinamide-rifampicin regimen.Methods and analysis: Adult patients with pulmonary TB admitted to six hospitals in Sweden and subjected to receive first-line treatment are included. Patients are randomised (1:3) to either 6-month standardised TB treatment or a 4-month regimen based on high-dose pyrazinamide (40 mg/kg) and rifampicin (35 mg/kg) along with standard doses of isoniazid and ethambutol. Plasma samples for measurement of drug exposure determined by liquid chromatography tandem-mass spectrometry are obtained at 0, 1, 2, 4, 6, 8, 12 and 24 hours, at day 1 and 14. Maximal drug concentration (C-max) and area under the concentration-time curve (AUC(0-24h)) are estimated by non-compartmental analysis. Conditions for early model-informed precision dosing of high-dose pyrazinamide-rifampicin are pharmacometrically explored. Adverse drug effects are monitored throughout the study and graded according to Common Terminology Criteria for Adverse Events V.5.0. Early bactericidal activity is assessed by time to positivity in BACTEC MGIT 960 of induced sputum collected at day 0, 5, 8, 15 and week 8. Minimum inhibitory concentrations of first-line drugs are determined using broth microdilution. Disease severity is assessed with X-ray grading and a validated clinical scoring tool (TBscore II). Clinical outcome is registered according to WHO definitions (2020) in addition to occurrence of relapse after end of treatment. Primary endpoint is pyrazinamide AUC(0-24h) and main secondary endpoint is safety.Ethics and dissemination: The study is approved by the Swedish Ethical Review Authority and the Swedish Medical Products Agency. Informed written consent is collected before study enrolment. The study results will be submitted to a peer-reviewed journal.
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12.
  • Miller, Frank, et al. (författare)
  • A decision theoretical modeling for Phase III investments and drug licensing
  • 2018
  • Ingår i: Journal of Biopharmaceutical Statistics. - : Informa UK Limited. - 1054-3406 .- 1520-5711. ; 28:4, s. 698-721
  • Tidskriftsartikel (refereegranskat)abstract
    • For a new candidate drug to become an approved medicine, several decision points have to be passed. In this article, we focus on two of them: First, based on Phase II data, the commercial sponsor decides to invest (or not) in Phase III. Second, based on the outcome of Phase III, the regulator determines whether the drug should be granted market access. Assuming a population of candidate drugs with a distribution of true efficacy, we optimize the two stakeholders' decisions and study the interdependence between them. The regulator is assumed to seek to optimize the total public health benefit resulting from the efficacy of the drug and a safety penalty. In optimizing the regulatory rules, in terms of minimal required sample size and the Type I error in Phase III, we have to consider how these rules will modify the commercial optimization made by the sponsor. The results indicate that different Type I errors should be used depending on the rarity of the disease.
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13.
  • Svensberg, Karin, et al. (författare)
  • Nordic Pharmacy Students' Opinions of their Patient Communication Skills Training
  • 2018
  • Ingår i: American Journal of Pharmaceutical Education. - : American Association of Colleges of Pharmacy (AACP). - 0002-9459 .- 1553-6467. ; 82:2, s. 152-165
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To describe Nordic pharmacy students' opinions of their patient communication skills training (PCST), and the association between course leaders' reports of PCST qualities and students' perceptions of their training. Secondary objective was to determine what factors influence these associations. Methods. A cross-sectional questionnaire-based study was performed. The various curricula were categorized into three types (basic, intermediate and innovative training) and students were divided into three groups according to the type of training they had received. Multivariable logistic regression models were fitted with different opinions as outcomes and three types of training as exposure, using generalized estimation equations. Results. There were 370 students who responded (response rate: 77%). Students within the innovative group were significantly more likely to agree that they had received sufficient training, and to agree with the assertion that the pharmacy school had contributed to their level of skills compared to students in the basic group. Conclusion. There appears to be an association between larger and varied programs of training in patient communication skills and positive attitudes toward this training on the part of the students, with students reporting that they received sufficient training, which likely enhanced their skills.
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14.
  • Tjäderborn, Micaela, 1983- (författare)
  • Psychoactive prescription drug use disorders, misuse and abuse : Pharmacoepidemiological aspects
  • 2016
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: There is a widespread and increasing use of psychoactive prescription drugs, such as opioid analgesics, anxiolytics, hypnotics and anti-epileptics, but their use is associated with a risk of drug use disorder, misuse and abuse. Today, these are globally recognized and emerging public health concerns.Aim: The aim of this thesis is to estimate the prevalence of psychoactive prescription drug (PPD) use disorders, misuse and abuse, and to investigate the association with some potential risk factors.Methods: A study using register data from forensic cause of death investigations investigated and described cases of fatal unintentional intoxication with tramadol (Study I). Based on register data on spontaneously reported adverse drug reactions (ADRs) reported cases of tramadol dependence were investigated and summarised (Study II). In a study in suspected drug-impaired drivers with a toxicology analysis confirming the intake of one out of five pre-specified PPDs, the prevalence of non-prescribed use was assessed and associated factors were investigated (Study III). From a cohort of patients initiating prescribed treatment with pregabalin, using data on prescription fills, a study investigated longitudinal utilisation patterns during five years with regards to use of the drug above the maximum approved daily dose (MAD), and factors associated with the utilisation patterns (Study IV).Results: In the first study, 17 cases of unintentional intoxications were identified, of which more concerned men, the median age was 44 years and the majority used multiple psychoactive substances (alcohol, illicit drugs and prescription drugs). The second study identified 104 spontaneously reported cases of tramadol dependence, in which more concerned women, the median age was 45 years, and a third reported a history of substance abuse and 40% of past psychoactive medication use. In the third study, more than half of the individuals suspected of drug-impaired driving used the drug without a recent prescription. Non prescribed use was most frequent in users of benzodiazepines and tramadol, and was more likely in younger individuals and in multiple-substance users. In the last paper five longitudinal utilisation patterns were found in pregabalin users, with two patterns associated with a particularly high risk of doses above the maximum approved dosing recommendation. This pattern of use was associated with male sex, younger age, non-urban residency and a recent prescribed treatment with an antiepileptic or opioid analgesic drug.Conclusions: This thesis shows that psychoactive prescription drug use disorders, misuse and abuse occur and may have serious and even fatal consequences. The prevalence varies between different drugs and populations. Abuse and misuse seem to be more common in young people. Fatal intoxications and misuse of prescribed drugs may be more common in men, while drug use disorders following prescribed treatment may be more common in women and non-prescribed use equally distributed between women and men. Individuals with a history of mental illness, substance use disorder or abuse, or of past use of psychoactive medications are likely important risk groups. In summary, the findings suggest a potential for improvements in the utilisation of psychoactive prescription drugs. The results may be useful in the planning of clinical and regulatory preventive interventions to promote the rational, individualised and safe use of such drugs.
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15.
  • Nijsingh, Niels, 1977, et al. (författare)
  • Managing pollution from antibiotics manufacturing: charting actors, incentives and disincentives
  • 2019
  • Ingår i: Environmental health. - : Springer Science and Business Media LLC. - 1476-069X. ; 18
  • Tidskriftsartikel (refereegranskat)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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16.
  • Saulo, Eleonor C., et al. (författare)
  • Willingness and ability to pay for artemisinin-based combination therapy in rural Tanzania
  • 2008
  • Ingår i: Malaria Journal. - London : BioMed Central. - 1475-2875. ; 7, s. 227-
  • Tidskriftsartikel (refereegranskat)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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17.
  • Essling, Elise, et al. (författare)
  • Pharmacy employees’ self-rated knowledge, use and attitudes toward homeopathy: A comparative survey in Sweden and Germany
  • 2019
  • Ingår i: European Pharmaceutical Journal. - : de Gruyter. - 2453-6725. ; 66:1, s. 19-27
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Homeopathy is being increasingly practiced within different medical areas of use. Homeopathic medicines are sold in German pharmacies, whereas the assortment of Swedish pharmacies does not include homeopathic medicines. Despite differences between Sweden and Germany, homeopathic medicines are classified as drugs in both countries. Objective: The aim of this study was to compare the pharmacy employees’ self-rated knowledge, use, and attitudes toward homeopathy in Sweden and Germany. Methods: A quantitative web survey was sent to 30 pharmacies in Sweden and 30 pharmacies in Germany, which were selected by using a multi-stage clustering sampling. The questionnaire contained closed-ended rating scales. To compare the self-rated knowledge, use, and attitudes toward homeopathy of Swedish and German pharmacy employees, chi-square tests and Mann-Whitney tests were performed in SPSS. Results: A total of 209 pharmacy employees answered the survey (108 in Sweden and 101 in Germany). German participants estimated their knowledge higher than the Swedish participants (p < 0.01). In both countries, most participants thought that pharmacy employees should have knowledge about homeopathy. Although most Swedish participants stated that they receive questions about homeopathy, the German pharmacy employees receive questions about homeopathy more frequently (p <0.01). Swedish participants reported less experience of own use of homeopathic medicines and less belief in their effectiveness as compared to the German participants (p < 0.01). However, in both countries, most participants stated that homeopathic medicines should be sold in pharmacies. Conclusion: As pharmacy employees should act professionally to advise customers on all drugs, increased homeopathic knowledge in pharmacy employees could potentially improve pharmaceutical practice.
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18.
  • Essling, Elise, et al. (författare)
  • Pharmacy employees’ self-rated knowledge, use and attitudes toward homeopathy: A comparative survey in Sweden and Germany
  • 2019
  • Ingår i: European Pharmaceutical Journal. - 2453-6725 .- 1338-6786. ; 66:1, s. 19-27
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Homeopathy is being increasingly practiced within different medical areas of use. Homeopathic medicines are sold in German pharmacies, whereas the assortment of Swedish pharmacies does not include homeopathic medicines. Despite differences between Sweden and Germany, homeopathic medicines are classified as drugs in both countries. Objective: The aim of this study was to compare the pharmacy employees’ self-rated knowledge, use, and attitudes toward homeopathy in Sweden and Germany. Methods: A quantitative web survey was sent to 30 pharmacies in Sweden and 30 pharmacies in Germany, which were selected by using a multi-stage clustering sampling. The questionnaire contained closed-ended rating scales. To compare the self-rated knowledge, use, and attitudes toward homeopathy of Swedish and German pharmacy employees, chi-square tests and Mann-Whitney tests were performed in SPSS. Results: A total of 209 pharmacy employees answered the survey (108 in Sweden and 101 in Germany). German participants estimated their knowledge higher than the Swedish participants (p < 0.01). In both countries, most participants thought that pharmacy employees should have knowledge about homeopathy. Although most Swedish participants stated that they receive questions about homeopathy, the German pharmacy employees receive questions about homeopathy more frequently (p <0.01). Swedish participants reported less experience of own use of homeopathic medicines and less belief in their effectiveness as compared to the German participants (p < 0.01). However, in both countries, most participants stated that homeopathic medicines should be sold in pharmacies. Conclusion: As pharmacy employees should act professionally to advise customers on all drugs, increased homeopathic knowledge in pharmacy employees could potentially improve pharmaceutical practice.
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19.
  • Sposato, Niklas S, et al. (författare)
  • Osteopathic Manipulative Treatment in Surgical Care: Short Review of Research Publications in Osteopathic Journals During the Period 1990 to 2017.
  • 2018
  • Ingår i: Journal of evidence-based integrative medicine. - : Sage Publications. - 2515-690X. ; 23
  • Forskningsöversikt (refereegranskat)abstract
    • A growing trend in surgical care is the investigation and incorporation of multimodal interventions into standardized programs. Additionally, manual therapies such as osteopathic manipulative treatment (OMT) are being used with patients in surgical care. Yet the scientific dialogue and the use of OMT in surgical care are currently insubstantial.The aim of this study was to present an overview of published research articles within the subject field of OMT in surgical care.Summative review of peer-reviewed research articles published in osteopathic journals during the period 1990 to 2017. In total, 10 articles were identified.Previous research has been conducted within the areas of abdominal, thoracic, gynecological, and/or orthopedic surgery with measured outcomes such as pain, analgesia consumption, length of hospital stay, and range of motion. Heterogeneity was identified in usage of osteopathic techniques, treatment duration, and occurrence, as well as in the treating osteopath's experience.Despite the small number of research articles within this field, both positive measured effects as well as the absence of such effects were identified. Overall, there was a heterogeneity concerning surgical contexts, diagnoses, signs and symptoms, as well as surgical phases in current interprofessional osteopathic publications. In this era of multimodal surgical care, we argue that there is an urgent need to evaluate OMT in this context of care and with a proper research approach.
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20.
  • Alrifaiy, Ahmed, et al. (författare)
  • A lab-on-a-chip for hypoxic patch clamp measurements combined with optical tweezers and spectroscopy : first investigations of single biological cells
  • 2015
  • Ingår i: Biomedical engineering online. - : Springer Science and Business Media LLC. - 1475-925X. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • The response and the reaction of the brain system to hypoxia is a vital research subject that requires special instrumentation. With this research subject in focus, a new multifunctional lab-on-a-chip (LOC) system with control over the oxygen content for studies on biological cells was developed. The chip was designed to incorporate the patch clamp technique, optical tweezers and absorption spectroscopy. The performance of the LOC was tested by a series of experiments. The oxygen content within the channels of the LOC was monitored by an oxygen sensor and verified by simultaneously studying the oxygenation state of chicken red blood cells (RBCs) with absorption spectra. The chicken RBCs were manipulated optically and steered in three dimensions towards a patch-clamp micropipette in a closed microfluidic channel. The oxygen level within the channels could be changed from a normoxic value of 18% O 2 to an anoxic value of 0.0-0.5% O 2. A time series of 3 experiments were performed, showing that the spectral transfer from the oxygenated to the deoxygenated state occurred after about 227 ± 1 s and a fully developed deoxygenated spectrum was observed after 298 ± 1 s, a mean value of 3 experiments. The tightness of the chamber to oxygen diffusion was verified by stopping the flow into the channel system while continuously recording absorption spectra showing an unchanged deoxygenated state during 5400 ± 2 s. A transfer of the oxygenated absorption spectra was achieved after 426 ± 1 s when exposing the cell to normoxic buffer. This showed the long time viability of the investigated cells. Successful patching and sealing were established on a trapped RBC and the whole-cell access (Ra) and membrane (Rm) resistances were measured to be 5.033 ± 0.412 M Ω and 889.7 ± 1.74 M Ω respectively.
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21.
  • Elobeid, Adila, et al. (författare)
  • Correlations Between Mini-Mental State Examination Score, Cerebrospinal Fluid Biomarkers, and Pathology Observed in Brain Biopsies of Patients With Normal-Pressure Hydrocephalus
  • 2015
  • Ingår i: Journal of Neuropathology and Experimental Neurology. - 0022-3069 .- 1554-6578. ; 74:5, s. 470-479
  • Tidskriftsartikel (refereegranskat)abstract
    • Alzheimer disease (AD)-related pathology was assessed in cortical biopsy samples of 111 patients with idiopathic normal-pressure hydrocephalus. Alzheimer disease hallmark lesions-beta-amyloid (A beta) and hyperphosphorylated tau (HPtau)-were observed in 47% of subjects, a percentage consistent with that for whole-brain assessment reported postmortem in unselected cohorts. Higher-immunostained area fraction of AD pathology corresponded with lower preoperative mini-mental state examination scores. Concomitant A beta and HPtau pathology, reminiscent of that observed in patients with AD, was observed in 22% of study subjects. There was a significant correlation between A beta-immunostained area fraction in tissue and A beta 42 (42-amino-acid form of A beta) in cerebrospinal fluid (CSF). Levels of A beta 42 were significantly lower in CSF in subjects with concomitant A beta and HPtau pathology compared with subjects lacking pathology. Moreover, a significant correlation between HPtau-immunostained area fraction and HPtau in CSF was noted. Both HPtau and total tau were significantly higher in CSF in subjects with concomitant A beta and HPtau pathology compared with subjects lacking pathology. The 42-amino-acid form of A beta (A beta 42) and HPtau in CSF were the most significant predictors of the presence of AD pathology in cortical biopsies. Long-term follow-up studies are warranted to assess whether all patients with idiopathic normal-pressure hydrocephalus with AD pathology progress to AD and to determine the pathologic substrate of idiopathic normal-pressure hydrocephalus.
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22.
  • Håkansson, Samuel, 1996, et al. (författare)
  • Potential for improved retention rate by personalized antiseizure medication selection: A register-based analysis
  • 2021
  • Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 62:9, s. 2123-2132
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective The first antiseizure medication (ASM) is ineffective or intolerable in 50% of epilepsy cases. Selection between more than 25 available ASMs is guided by epilepsy factors, but also age and comorbidities. Randomized evidence for particular patient subgroups is seldom available. We asked whether register data could be used for retention rate calculations based on demographics, comorbidities, and ASM history, and quantified the potential improvement in retention rates of the first ASM in several large epilepsy cohorts. We also describe retention rates in patients with epilepsy after traumatic brain injury and dementia, patient groups with little available evidence. Methods We used medical, demographic, and drug prescription data from epilepsy cohorts from comprehensive Swedish registers, containing 6380 observations. By analyzing 381 840 prescriptions, we studied retention rates of first- and second-line ASMs for patients with epilepsy in multiple sclerosis (MS), brain infection, dementia, traumatic brain injury, or stroke. The rank of retention rates of ASMs was validated by comparison to published randomized control trials. We identified the optimal stratification for each brain disease, and quantified the potential improvement if all patients had received the optimal ASM. Results Using optimal stratification for each brain disease, the potential improvement in retention rate (percentage points) was MS, 20%; brain infection, 21%; dementia, 14%; trauma, 21%; and stroke, 14%. In epilepsy after trauma, levetiracetam had the highest retention rate at 80% (95% confidence interval [CI] = 65-89), exceeding that of the most commonly prescribed ASM, carbamazepine (p = .04). In epilepsy after dementia, lamotrigine (77%, 95% CI = 68-84) and levetiracetam (74%, 95% CI = 68-79) had higher retention rates than carbamazepine (p = .006 and p = .01, respectively). Significance We conclude that personalized ASM selection could improve retention rates and that national registers have potential as big data sources for personalized medicine in epilepsy.
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23.
  • Alin, Rebecca, 1989, et al. (författare)
  • A Preparatory Study for a Randomized Controlled Trial of Dietary Fiber Intake During Adult Pelvic Radiotherapy
  • 2021
  • Ingår i: Frontiers in Nutrition. - : Frontiers Media SA. - 2296-861X. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Patients undergoing pelvic radiotherapy are often advised to omit fiber-rich foods from their diet to reduce the adverse effects of treatment. Scientific evidence supporting this recommendation is lacking, and recent studies on animals and humans have suggested that there is a beneficial effect of dietary fiber for the alleviation of symptoms. Randomized controlled studies on dietary fiber intake during pelvic radiotherapy of sufficient size and duration are needed. As preparation for such a large-scale study, we evaluated the feasibility, compliance, participation rate, and logistics and report our findings here in this preparatory study. Methods: In this preparatory study of a fiber intervention trial, Swedish gynecological cancer patients scheduled for radiotherapy were recruited between January 2019 and August 2020. During the intervention, the participants filled out questionnaires and used an application. They also consumed a fiber supplement at first in powder form, later in capsules. Blood- and fecal samples were collected. The study is registered in clinicaltrials.gov (https://clinicaltrials.gov/ct2/show/NCT04534075?cond=fidura&draw=2&rank=1). Results: Among 136 approached patients, 57 started the study and the participation rate for primary outcomes was 63% (third blood sample) and 65% (third questionnaire). Barely half of the participants provided fecal samples. Providing concise and relevant information to the patients at the right time was crucial in getting them to participate and stay in the study. The most common reasons for declining participation or dropping out were the expected burden of radiotherapy or acute side effects. Tailoring the ambition level to each patient concerning the collection of data beyond the primary endpoints was an important strategy to keep the dropout rate at an acceptable level. Using capsules rather than psyllium in powder form made it much easier to document intake and to create a control group. During the course of the preparatory study, we improved the logistics and for the last 12 participants included, the participation rate was 100% for the earliest primary outcome. Conclusion: A variety of adjustments in this preparatory study resulted in an improved participation rate, which allowed us to set a final protocol and proceed with the main study.
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24.
  • Bärkås, Annika, et al. (författare)
  • Analysis of Voluntary User Feedback of the Swedish National PAEHR Service
  • 2019
  • Ingår i: MEDINFO 2019. - : IOS Press. - 9781643680033 - 9781643680026 ; 264, s. 1126-1130
  • Konferensbidrag (refereegranskat)abstract
    • "Journalen" is a patient accessible electronic health record (PAEHR) and the national eHealth service for Sweden's citizens to gain access to their EHR. The Swedish national eHealth organization Inera, responsible for Journalen, created an inbox to receive voluntary user feedback about Journalen in order to improve the service from the user perspective. Based on voluntary user feedback via email. This study explored patients' experiences of using the national eHealth service and identified pros and cons. A mixed method content analysis was performed. In total, 1084 emails from 2016-2017 have been analyzed. 9 categories were identified, the most frequent ones related to questions about why some information was not accessible (due to regional differencies), feedback (including only positive or negative comments as well as constructive improvement suggestions), and emails about errors that user found in their record. These data can be successfully used to continuously improve an already implemented eHealth service.
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25.
  • Pestoff, Rebecka, et al. (författare)
  • Genetic counsellors in Sweden : their role and added value in the clinical setting.
  • 2016
  • Ingår i: European Journal of Human Genetics. - : Nature Publishing Group. - 1018-4813 .- 1476-5438. ; 24:3, s. 350-355
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic testing is becoming more commonplace in general and specialist health care and should always be accompanied by genetic counselling, according to Swedish law. Genetic counsellors are members of the multi-disciplinary team providing genetic counselling. This study examined the role and added value of genetic counsellors in Sweden, using a cross-sectional on-line survey. The findings showed that the genetic counsellors added value in the clinical setting by acting as the 'spider-in-the-web' regarding case management, having a more holistic, ethical and psychological perspective, being able to offer continuous support and build a relationship with the patient, and being more accessible than medical geneticists. The main difference between a genetic counsellor and medical geneticist was that the doctor had the main medical responsibility. Thus genetic counsellors in Sweden contribute substantially to the care of patients in the clinical genetic setting.
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26.
  • Tate, David J., et al. (författare)
  • Curriculum for training in endoscopic mucosal resection in the colon : European Society of Gastrointestinal Endoscopy (ESGE) Position Statement
  • 2023
  • Ingår i: Endoscopy. - 0013-726X. ; 55:7, s. 645-679
  • Tidskriftsartikel (refereegranskat)abstract
    • Main recommendations: Endoscopic mucosal resection (EMR) is the standard of care for the complete removal of large (≥ 10mm) nonpedunculated colorectal polyps (LNPCPs). Increased detection of LNPCPs owing to screening colonoscopy, plus high observed rates of incomplete resection and need for surgery call for a standardized approach to training in EMR. 1 Trainees in EMR should have achieved basic competence in diagnostic colonoscopy, < 10-mm polypectomy, pedunculated polypectomy, and common methods of gastrointestinal endoscopic hemostasis. The role of formal training courses is emphasized. Training may then commence in vivo under the direct supervision of a trainer. 2 Endoscopy units training endoscopists in EMR should have specific processes in place to support and facilitate training. 3 A trained EMR practitioner should have mastered theoretical knowledge including how to assess an LNPCP for risk of submucosal invasion, how to interpret the potential difficulty of a particular EMR procedure, how to decide whether to remove a particular LNPCP en bloc or piecemeal, whether the risks of electrosurgical energy can be avoided for a particular LNPCP, the different devices required for EMR, management of adverse events, and interpretation of reports provided by histopathologists. 4 Trained EMR practitioners should be familiar with the patient consent process for EMR. 5 The development of endoscopic non-technical skills (ENTS) and team interaction are important for trainees in EMR. 6 Differences in recommended technique exist between EMR performed with and without electrosurgical energy. Common to both is a standardized technique based upon dynamic injection, controlled and precise snare placement, safety checks prior to the application of tissue transection (cold snare) or electrosurgical energy (hot snare), and interpretation of the post-EMR resection defect. 7 A trained EMR practitioner must be able to manage adverse events associated with EMR including intraprocedural bleeding and perforation, and post-procedural bleeding. Delayed perforation should be avoided by correct interpretation of the post-EMR defect and treatment of deep mural injury. 8 A trained EMR practitioner must be able to communicate EMR procedural findings to patients and provide them with a plan in case of adverse events after discharge and a follow-up plan. 9 A trained EMR practitioner must be able to detect and interrogate a post-endoscopic resection scar for residual or recurrent adenoma and apply treatment if necessary. 10 Prior to independent practice, a minimum of 30 EMR procedures should be performed, culminating in a trainer-guided assessment of competency using a validated assessment tool, taking account of procedural difficulty (e. g. using the SMSA polyp score). 11 Trained practitioners should log their key performance indicators (KPIs) of polypectomy during independent practice. A guide for target KPIs is provided in this document.
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27.
  • Abdulkadir, Sazan Abass, et al. (författare)
  • Potential Drug-Related Problems in Pediatric Patients-Describing the Use of a Clinical Decision Support System at Pharmacies in Sweden
  • 2023
  • Ingår i: Pharmacy. - : MDPI. - 2226-4787. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The clinical support system Electronic Expert Support (EES) is available at all pharmacies in Sweden to examine electronic prescriptions when dispensing to prevent drug-related problems (DRPs). DRPs are common, and result in patient suffering and substantial costs for society. The aim of this research was to study the use of EES for the pediatric population (ages 0-12 years), by describing what types of alerts are generated for potential DRPs, how they are handled, and how the use of EES has changed over time. Data on the number and categories of EES analyses, alerts, and resolved alerts were provided by the Swedish eHealth Agency. The study shows that the use of EES has increased. The most common type of alert for a potential DRP among pediatric patients was regarding high doses in children (30.3% of all alerts generated). The most common type of alert for a potential DRP that was resolved among pediatrics was therapy duplication (4.6% of the alerts were resolved). The most common reason for closing an alert was dialogue with patient for verification of the treatment (66.3% of all closed alerts). Knowledge of which type of alerts are the most common may contribute to increased prescriber awareness of important potential DRPs.
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28.
  • Beer, Netta, et al. (författare)
  • Scenarios for 3D printing of personalized medicines : A case study
  • 2021
  • Ingår i: Exploratory Research in Clinical and Social Pharmacy. - : Elsevier. - 2667-2766. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background3D printing is a promising new technology for medicines' production. It employs additive manufacturing techniques, and is ideal for producing personalized medicines (e.g., patient-tailored dose, dosage form, drug release kinetics).ObjectiveTo investigate how 3D printing technologies can be implemented in a European pharmaceutical system, by suggesting different scenarios and assessing aspects that could affect its implementation.MethodQualitative, semi-structured interviews were conducted with key stakeholders (e.g., from ministry, authorities, research organizations, pharmacies) in the Netherlands to elicit perspectives on 3D printing of personalized medicines. The Netherlands were chosen since it has a strong tradition in compounding. Five general scenarios were investigated: placing the 3D printers in industry, community pharmacies, hospital pharmacies, compounding facilities, and in patients' homes. Content analysis was used, building on verbatim transcripts.ResultsFifteen stakeholders were interviewed. Regulatory, economic, ethical and organizational challenges were identified to varying degrees in the different scenarios. The industry and home scenarios were associated with the most challenges, hospital pharmacies and compounding facilities with the least. Other important aspects identified were the role of community pharmacies, and who should design the tablets to be printed.ConclusionAll potential scenarios for 3D printing of personalized medicines include challenges. These should be taken into account when pursuing the use of 3D printing of medicine.
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29.
  • Bertilsson, Emma, et al. (författare)
  • Pharmacists experience of and perspectives about recruiting patients into a community pharmacy asthma service trial
  • 2021
  • Ingår i: Research in Social and Administrative Pharmacy. - : Elsevier. - 1551-7411 .- 1934-8150. ; 17:3, s. 595-605
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Research trials testing the impact of community pharmacy services require adequate and appropriate recruitment of patients by participating pharmacists, however, this step presents an ongoing challenge. Objective: To identify factors affecting recruitment of patients in community pharmacies participating in a multi-center trial of a pharmacy asthma service in Australia (Pharmacy Trial Program - Asthma and Rhinitis Control (PTP-ARC). Methods: The PTP-ARC protocol required identification and recruitment of seven eligible asthma patients per pharmacy. Pharmacists responsible for sites that failed to recruit or retain any patients into the PTP-ARC trial participated in a semi-structured telephone interview about their experiences with these elements of the trial. The interviews were recorded, transcribed and coded using QSR International's NVivo 11 software. The analysis was conducted with reference to the COM-B framework (Capability, Opportunity, Motivation). Results: Pharmacists from 47 of 50 eligible pharmacies were interviewed. Seventeen factors were isolated and mapped to the COM-B framework. Psychological capability (recruitment hesitancy, research literacy and health literacy), physical capability (technological barriers, staffing issues and pharmacy busyness), physical opportunity (patient busyness, trial timing, study protocol, support and location), social opportunity (health literacy and supportive milieu), reflective motivation (incentive for participation, simplification) and automatic motivation (patient attitudes and pharmacist-felt experience) were factors affecting pharmacists' participation. Challenges identified included: issues with the software, unfamiliarity with research procedures generally (and specifically with the PTP-ARC protocols), the patients' lack of interest and pharmacists' lack of time. Conclusions: To the best of our knowledge, this is the first study to focus on issues affecting patient recruitment into a pharmacy health services (asthma) trial in real time. To propel evidence-based trials towards practice implementation, user-friendly software, pharmacists' training on research and patient-engagement and adequate remuneration to address pharmacist time issues need to be key foci for health services design and implementation research.
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30.
  • Bonner, Stephen, et al. (författare)
  • A review of biomedical datasets relating to drug discovery: a knowledge graph perspective
  • 2022
  • Ingår i: Briefings in Bioinformatics. - : Oxford University Press (OUP). - 1467-5463 .- 1477-4054. ; In Press
  • Forskningsöversikt (refereegranskat)abstract
    • Drug discovery and development is a complex and costly process. Machine learning approaches are being investigated to help improve the effectiveness and speed of multiple stages of the drug discovery pipeline. Of these, those that use Knowledge Graphs (KG) have promise in many tasks, including drug repurposing, drug toxicity prediction and target gene-disease prioritization. In a drug discovery KG, crucial elements including genes, diseases and drugs are represented as entities, while relationships between them indicate an interaction. However, to construct high-quality KGs, suitable data are required. In this review, we detail publicly available sources suitable for use in constructing drug discovery focused KGs. We aim to help guide machine learning and KG practitioners who are interested in applying new techniques to the drug discovery field, but who may be unfamiliar with the relevant data sources. The datasets are selected via strict criteria, categorized according to the primary type of information contained within and are considered based upon what information could be extracted to build a KG. We then present a comparative analysis of existing public drug discovery KGs and an evaluation of selected motivating case studies from the literature. Additionally, we raise numerous and unique challenges and issues associated with the domain and its datasets, while also highlighting key future research directions. We hope this review will motivate KGs use in solving key and emerging questions in the drug discovery domain.
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31.
  • Centanni, Maddalena, 1994- (författare)
  • Model-based evaluation of biomarkers for dose-individualization in oncology
  • 2024
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • In contemporary cancer care, several issues are garnering increasing attention. First, significant inter-individual variability among patients challenges the effectiveness of a uniform dosing approach. Second, the escalating costs of treatments necessitate careful consideration when selecting doses and other clinical modalities, including biomarkers, while balancing economic constraints. The objective of this thesis was to evaluate techniques for tailoring doses and guiding clinical decisions for cancer patients through the development and implementation of various models, with the aim of improving treatment outcomes in terms of both efficacy and safety. Through a model-based framework integrating sunitinib pharmacokinetics (PK), adverse events, biomarkers, tumor dynamics and their correlation with overall survival, different treatment schedules and biomarkers for dose individualization were explored. Based on the proposed threshold values, neutrophil count (ANC) and the biomarker sVEGFR-3 were identified as offering the best balance between safety and efficacy for sunitinib in gastro-intestinal stromal tumors (GIST) and could thus serve as viable guides for dose individualization in clinical practice. Given its routine measurement, dose adjustments guided by ANC may be preferable in clinical settings. The feasibility of utilizing diastolic blood pressure (dBP) for personalized dose optimization of tyrosine-kinase inhibitors in clinical settings is constrained due to its reliance on repeated measurements taken at consistent intervals. For axitinib and sunitinib, model-based predictions using multiple clinical measurements were more accurate than single sample measurements. For drugs with high unexplained inter-individual variability (IIV), low residual variability (RUV), and low inter-occasional variability (IOV), therapeutic drug monitoring (TDM) provided a more accurate measure of exposure. Conversely, for drugs with low IIV and high RUV and IOV, pharmacogenetic profiling was more suitable. However, the prevalence of pharmacogenetic subtypes and the challenge of measuring exposure metrics like AUC through limited sampling also influence these approaches.This research further emphasizes how model structure affects the outcomes of cost-effectiveness analyses and consequently the potential implications for regulatory decisions. Although creating mechanistic models for these analyses demands substantial initial effort, the growing need for model-based analyses in drug approval is likely to make these models more accessible for future compounds. Moreover, such models are expected to be more biologically plausible and therefore more reflective of reality and offer flexibility for exploring alternative dosages with limited additional effort.Using model-based assessments, the relationship between the PK and PK-pharmacodynamic (PKPD) profiles of adverse events arising from therapies for acute lymphocytic leukemia were established. For PEG-asparaginase, the PK model categorized 93% of patients who experienced inactivation against PEG-asparaginase as having an increased clearance, and 86% of patients who did not experience hypersensitivity as maintaining stable clearance throughout their asparaginase treatment. This approach marks a potential method for predicting inactivation by identifying early changes in clearance. For vincristine, model-informed precision dosing was shown to reduce the incidence of vincristine-induced peripheral neuropathy (VIPN) from 62.1% to 53.9%, though the clinical impact remains modest.
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32.
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33.
  • Forbes, Carol A., et al. (författare)
  • A systematic literature review comparing methods for the measurement of patient persistence and adherence
  • 2018
  • Ingår i: Current Medical Research and Opinion. - : Taylor & Francis Group. - 0300-7995 .- 1473-4877. ; 34:9, s. 1613-1625
  • Forskningsöversikt (refereegranskat)abstract
    • Objectives: A systematic literature review was conducted comparing different approaches estimating persistence and adherence in chronic diseases with polypharmacy of oral and subcutaneous treatments. Methods: This work followed published guidance on performing systematic reviews. Twelve electronic databases and grey literature sources were used to identify studies and guidelines for persistence and adherence of oral and subcutaneous therapies in hypercholesterolemia, type 2 diabetes, hypertension, osteoporosis and rheumatoid arthritis. Outcomes of interest of each persistence and adherence data collection and calculation method included pros: accurate, easy to use, inexpensive; and cons: inaccurate, difficult to use, expensive. Results: A total of 4158 records were retrieved up to March 2017. We included 16 observational studies, 5 systematic reviews and 7 guidelines, in patients with hypercholesterolemia (n=8), type 2 diabetes (n=4), hypertension (n=2), rheumatoid arthritis (n=1) and mixed patient populations (n=13). Pharmacy and medical records offer an accurate, easy and inexpensive data collection method. Pill count, medication event monitoring systems (MEMs), self-report questionnaires and observer report are easy to use. MEMS and biochemical monitoring tests can be expensive. Proportion of days covered (PDC) was recommended as a gold standard calculation method for long-term treatments. PDC avoids use of days' supply in calculation, hence is more accurate compared to medication possession ratio (MPR) to assess adherence to treatments in chronic diseases. Conclusions: Decisions on what method to use should be based on considerations of the route of medication administration, the resources available, setting and aim of the assessment. Combining different methods may provide wider insights into adherence and persistence, including patient behavior.
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34.
  • Forslund, Sofia K., et al. (författare)
  • Combinatorial, additive and dose-dependent drug–microbiome associations
  • 2021
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 600:7889, s. 500-505
  • Tidskriftsartikel (refereegranskat)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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35.
  • Frisk, Pia, et al. (författare)
  • Utilisation of prescription and over-the-counter triptans : a cross-sectional study in Stockholm, Sweden
  • 2016
  • Ingår i: European Journal of Clinical Pharmacology. - : Springer. - 0031-6970 .- 1432-1041. ; 72:6, s. 747-754
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Triptans are widely used in acute migraine, and in some countries, they are also available over-the-counter (OTC). In Sweden, sales have increased for both prescription and OTC triptans. This study aimed to describe current prescribing and utilisation patterns of prescription and OTC triptans in Stockholm, Sweden.METHODS: Register data from 4759 patients dispensed triptans in 2014 were used to study documented diagnosis of migraine, concomitant acute and preventive treatment for migraine, and contraindications. Survey data from 49 patients purchasing OTC triptans in three pharmacies were used to capture physician-diagnosed migraine, concomitant acute and preventive treatment for migraine, a behaviour of combining or alternating between prescription and OTC triptans, and pharmacy counselling rates.RESULTS: Among the prescription triptan users, 52 % had a recorded diagnosis of migraine, 48 % had no other acute treatment, preventive treatment was rare (12 %) and contraindications were found in 2 % of the patients. Among the OTC triptan users, the majority (63 %) had been diagnosed by a physician and had a history of prescription triptan use, but combining or alternating between OTC and prescription triptans was rare. Concomitant acute treatment was reported in 53 % and preventive treatment was rare (4 %), despite high self-reported migraine frequencies. Some off-label use was detected, despite moderate to high counselling rates.CONCLUSION: Triptans are prescribed with attention to safety but with poor recording of migraine diagnosis. OTC triptan users generally have a history of prescription triptan use. Preventive treatment rates are low in both groups. Strategies to discern patients who need other treatment options should be considered.
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36.
  • Hammar, Tora, 1984-, et al. (författare)
  • Discrepancies in patients' medication lists from pharmacies in Sweden : an interview study before the implementation of the Swedish National Medication List
  • 2023
  • Ingår i: International Journal of Clinical Pharmacy. - : Springer. - 2210-7703 .- 2210-7711. ; 45, s. 88-96
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Discrepancies in medication lists are common and can contribute to drug-related problems. This study was performed before the implementation of the National Medication List in Sweden, an intervention expected to improve the accuracy of medication lists. Aim The aim of the study was to examine the number and type of discrepancies in the medication list from pharmacies in Sweden. The secondary aim was to describe the information sources Swedish patients used as their medication lists and how confident they were with the information. Method Structured interviews were conducted with patients at 13 community pharmacies in Sweden during the period October 5, 2020, to April 16, 2021. The printed medication list was reviewed together with the patient to identify any discrepancies and missing information. Results A total of 327 patients were included in the study (response rate 51%). The printed medication list from pharmacies was the most common information source for patients to know which medications to use. Two thirds (n = 215) of the patients had at least one discrepancy among their prescriptions and 32% (n = 106) were missing at least one prescription medication. Among all prescriptions (n = 2567) 10% (n = 264) were non-current prescriptions, 9% (n = 238) were duplicates and 3% (n = 88) had the wrong dose. The proportion of prescriptions with discrepancies differed between drug-groups. Conclusion The discrepancies described in this study can have serious consequences, and results provide a baseline for studies after the implementation of the National Medication List.
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37.
  • Hellström, Lina, 1975-, et al. (författare)
  • Clinical implementation of systematic medication reconciliation and review as part of the Lund Integrated Medicines Management model – impact on all cause emergency department revisits
  • 2012
  • Ingår i: Journal of Clinical Pharmacy and Therapeutics. - : Hindawi Limited. - 0269-4727 .- 1365-2710. ; 37:6, s. 686-692
  • Tidskriftsartikel (refereegranskat)abstract
    • What is known and objective: Interventions involving medication reconciliation and review by clinical pharmacists can reduce drug-related problems and improve therapeutic outcomes. The objective of this study was to examine the impact of routine admission medication reconciliation and inpatient medication review on emergency department (ED) revisits after discharge. Secondary outcomes included the combined rate of post-discharge hospital revisits or death.Methods: This prospective, controlled study included all patients hospitalised in three internal medicine wards in a university hospital, between January 1 2006 and May 31 2008. Medication reconciliation on admission and inpatient medication review, conducted by clinical pharmacists in a multiprofessional team, were implemented in these wards at different times during 2007 and 2008 (intervention periods). A discharge medication reconciliation was undertaken in all the study wards, during both control and intervention periods. Patients were included in the intervention group (n=1216) if they attended a ward with medication reconciliation and review, whether they had received the intervention or not. Control patients (n=2758) attended the wards before implementation of the intervention.  Results: No impact of medication reconciliation and reviews on ED revisits (hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.86-1.04) or event-free survival (HR, 0.96; 95% CI, 0.88-1.04) was demonstrated. In the intervention group, 594 patients (48.8%) visited the ED, compared to 1416 (51.3%) control patients. In total, 716 intervention (58.9%) and 1688 (61.2%) control patients experienced any event (ED visit, hospitalisation or death). Because the time to a subsequent ED visit was longer for the control as well as the intervention groups in 2007 than in 2006 (p<0.05), we re-examined this cohort of patients; the proportion of patients revisiting the ED was similar in both groups in 2007 (p=0.608).What is new and conclusion: Routine implementation of medication reconciliation and reviews on admission and during the hospital stay did not appear to have any impact on ED revisits, rehospitalisations or mortality over six months' follow-up.  
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38.
  • Hellström, Lina, 1975-, et al. (författare)
  • Errors in medication history at hospital admission: prevalence and predicting factors
  • 2012
  • Ingår i: BMC Clinical Pharmacology. - : Springer Science and Business Media LLC. - 1472-6904. ; 12, s. Article ID: 9-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: An accurate medication list at hospital admission is essential for the evaluation and further treatment of patients. The objective of this study was to describe the frequency, type and predictors of errors in medication history, and to evaluate the extent to which standard care corrects these errors.Methods:A descriptive study was carried out in two medical wards in a Swedish hospital using Lund Integrated Medicines Management (LIMM)-based medication reconciliation. A clinical pharmacist identified each patient's most accurate pre-admission medication list by conducting a medication reconciliation process shortly after admission. This list was then compared with the patient's medication list in the hospital medical records. Addition or withdrawal of a drug or changes to the dose or dosage form in the hospital medication list were considered medication discrepancies. Medication discrepancies for which no clinical reason could be identified (unintentional changes) were considered medication history errors.Results: The final study population comprised 670 of 818 eligible patients. At least one medication history error was identified by pharmacists conducting medication reconciliations for 313 of these patients (47%; 95% CI 43-51%). The most common medication error was an omitted drug, followed by a wrong dose. Multivariate logistic regression analysis showed that a higher number of drugs at admission (odds ratio [OR] per 1 drug increase = 1.10; 95% CI 1.06 - 1.14; p<0.0001) and the patient living in their own home without any care services (OR1.58; 95% CI 1.02 - 2.45; p = 0.042) were predictors for medication history errors at admission. The results further indicated that standard care by non-pharmacist ward staff had partly corrected the errors in affected patients by four days after admission, but a considerable proportion of the errors made in the initial medication history at admission remained undetected by standard care (OR for medication errors detected by pharmacists' medication reconciliation carried out on days 4 - 11 compared to days 0 - 1 = 0.52; 95% CI 0.30 - 0.91; p = 0.021).Conclusions: Clinical pharmacists conducting LIMM-based medication reconciliations have a high potential for correcting errors in medication history for all patients. In an older Swedish population, those prescribed many drugs seem to benefit most from admission medication reconciliation.
  •  
39.
  • Hughes, Carmel M, et al. (författare)
  • Provision of pharmaceutical care by community pharmacists : a comparison across Europe
  • 2010
  • Ingår i: Pharmacy World & Science. - : Springer Science and Business Media LLC. - 0928-1231 .- 1573-739X. ; 32:4, s. 472-487
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To investigate the provision of pharmaceutical care by community pharmacists across Europe and to examine the various factors that could affect its implementation. Methods A questionnaire-based survey of community pharmacies was conducted within 13 European countries. The questionnaire consisted of two sections. The first section focussed on demographic data and services provided in the pharmacy. The second section was a slightly adapted version of the Behavioral Pharmaceutical Care Scale (BPCS) which consists of three main dimensions (direct patient care activities, referral and consultation activities and instrumental activities). Results Response rates ranged from 10–71% between countries. The mean total score achieved by community pharmacists, expressed as a percentage of the total score achievable, ranged from 31.6 (Denmark) to 52.2% (Ireland). Even though different aspects of pharmaceutical care were implemented to different extents across Europe, it was noted that the lowest scores were consistently achieved in the direct patient care dimension (particularly those related to documentation, patient assessment and implementation of therapeutic objectives and monitoring plans) followed by performance evaluation and evaluation of patient satisfaction. Pharmacists who dispensed higher daily numbers of prescriptions in Ireland, Germany and Switzerland had significantly higher total BPCS scores. In addition, pharmacists in England and Ireland who were supported in their place of work by other pharmacists scored significantly higher on referral and consultation and had a higher overall provision of pharmaceutical care. Conclusion The present findings suggest that the provision of pharmaceutical care in community pharmacy is still limited within Europe. Pharmacists were routinely engaged in general activities such as patient record screening but were infrequently involved in patient centred professional activities such as the implementation of therapeutic objectives and monitoring plans, or in self-evaluation of performance.
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40.
  • Janssens, Rosanne, et al. (författare)
  • How can patient preferences be used and communicated in the regulatory evaluation of medicinal products? : Findings and recommendations from IMI PREFER and call to action
  • 2023
  • Ingår i: Frontiers in Pharmacology. - : Frontiers Media S.A.. - 1663-9812. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Patients have unique insights and are (in-)directly affected by each decision taken throughout the life cycle of medicinal products. Patient preference studies (PPS) assess what matters most to patients, how much, and what trade-offs patients are willing to make. IMI PREFER was a six-year European public-private partnership under the Innovative Medicines Initiative that developed recommendations on how to assess and use PPS in medical product decision-making, including in the regulatory evaluation of medicinal products. This paper aims to summarize findings and recommendations from IMI PREFER regarding i) PPS applications in regulatory evaluation, ii) when and how to consult with regulators on PPS, iii) how to reflect PPS in regulatory communication and iv) barriers and open questions for PPS in regulatory decision-making.Methods: PREFER performed six literature reviews, 143 interviews and eight focus group discussions with regulators, patient representatives, industry representatives, Health Technology Assessment bodies, payers, academics, and clincians between October 2016 and May 2022.Results: i) With respect to PPS applications, prior to the conduct of clinical trials of medicinal products, PPS could inform regulators' understanding of patients' unmet needs and relevant endpoints during horizon scanning activities and scientific advice. During the evaluation of a marketing authorization application, PPS could inform: a) the assessment of whether a product meets an unmet need, b) whether patient-relevant clinical trial endpoints and outcomes were studied, c) the understanding of patient-relevant effect sizes and acceptable trade-offs, and d) the identification of key (un-)favorable effects and uncertainties. ii) With respect to consulting with regulators on PPS, PPS researchers should ideally have early discussions with regulators (e.g., during scientific advice) on the PPS design and research questions. iii) Regarding external PPS communication, PPS could be reflected in the assessment report and product information (e.g., the European Public Assessment Report and the Summary of Product Characteristics). iv) Barriers relevant to the use of PPS in regulatory evaluation include a lack of PPS use cases and demonstrated impact on regulatory decision-making, and need for (financial) incentives, guidance and quality criteria for implementing PPS results in regulatory decision-making. Open questions concerning regulatory PPS use include: a) should a product independent broad approach to the design of PPS be taken and/or a product-specific one, b) who should optimally be financing, designing, conducting, and coordinating PPS, c) when (within and/or outside clinical trials) to perform PPS, and d) how can PPS use best be operationalized in regulatory decisions.Conclusion: PPS have high potential to inform regulators on key unmet needs, endpoints, benefits, and risks that matter most to patients and their acceptable trade-offs. Regulatory guidelines, templates and checklists, together with incentives are needed to foster structural and transparent PPS submission and evaluation in regulatory decision-making. More PPS case studies should be conducted and submitted for regulatory assessment to enable regulatory discussion and increase regulators' experience with PPS implementation and communication in regulatory evaluations.
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41.
  • Jowkar, Nima, et al. (författare)
  • A Presentation of Central Communication Aspects in the Patient-Provider Relationship-Potential Learnings for Community Pharmacists
  • 2020
  • Ingår i: Pharmacy. - : MDPI. - 2226-4787. ; 8:4
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Several studies have shown that communication between patients and HCPs is still not optimal in integrating patients' perspectives on how best to manage their diseases and their medication. One such area where encounters between patients and professionals still needs to develop to better incorporate the patient's perspective is pharmacy practice. The aim of this study was therefore to explore and present new typologies and communication aspects of HCP-patient relationships since a comprehensive literature search in 1997 conducted by Sondell and Soderfeldt, and relate the findings to pharmacy practice. In total, 11 articles were identified by applying the techniques of a purposeful literature search. The articles covered aspects of: shifting and adapting roles during the encounter, techniques to ensure individualizing in the encounter, avoiding inappropriate routines, coping with internet-informed patients, achieving mutual goals, dealing with uncertainty including avoiding rigid preconceptions, using social conversation, incorporating patients' prior experiences, aligning language, adapting greetings and exploring the cultures and communication patterns of patients from other ethnic backgrounds. The variety of these communication aspects points to the immense complexity of communication as a practice discipline. This article has presented some of the literature that pharmacists can consult, in the endeavor of improving their communication practices.
  •  
42.
  • Jönsson, Anna K, et al. (författare)
  • Influence of refill adherence method when comparing level of adherence for different dosing regimens
  • 2014
  • Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 70:5, s. 589-597
  • Tidskriftsartikel (refereegranskat)abstract
    • To examine the impact of two methods when estimating refill adherence in patients using bisphosphonates with different dosing regimens. In the Swedish Prescribed Drug Register, 18,203 new users of bisphosphonates aged 18-85 years were identified between 1 July 2006 and 30 June 2007 and followed for a maximum of 2 years. The patients were categorised based on dosing regimen: one tablet daily, one tablet weekly, switching between these regimens, and other regimens. Refill adherence was estimated with Continuous measure of Medication Acquisition (CMA, adherent if CMA a parts per thousand yenaEuro parts per thousand 80 %) and the maximum gap method (adherent if gaps < 45 days). Differences in adherence between patients in the groups were assessed with logistic regression models controlling for confounding factors. The proportion of patients classified as adherent was higher using CMA compared with patients classified as adherent using the maximum gap method. Patients on one tablet weekly had significantly lower adherence compared with patients on one tablet daily in the main analyses of both methods (the maximum gap method: 73 % vs. 80 %; adjusted OR = 0.71; 95 % CI 0.57-0.89 and CMA: 84 % vs. 88 %, adjusted OR = 0.75; 95 % CI 0.57-0.99). Patients using the other two dosing regimens had significantly lower adherence compared with patients on one tablet daily using both methods. Choice of method has an impact on the estimates of refill adherence to bisphosphonates. Patients on one tablet weekly dosing had lower adherence compared with patients on one tablet daily dosing using both methods.
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43.
  • Krigsman, Kristin, et al. (författare)
  • Refill non-adherence to repeat prescriptions leads to treatment gaps or to high extra costs.
  • 2007
  • Ingår i: Pharmacy World & Science. - : Springer Netherlands. - 0928-1231 .- 1573-739X. ; 29:1, s. 19-24
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To determine the nature and extent of undersupply and the economic consequences of oversupply of medication among non-adherent patients. METHODS: This study used copies of repeat prescriptions (= multiple dispensations), collected during 1 week in 2002 at 16 Swedish community pharmacies. For patients with a refill adherence below 80%, treatment gaps were defined as the number of days they had no drug available. The cost of drug oversupply (i.e., refill adherence > 120%) was calculated from the prices of the drug packages dispensed. RESULTS: The number of collected repeat prescriptions was 3,636. The median of treatment gaps among patients with a refill adherence below 80% was 53 days per 90-100 days treatment period and the corresponding median for oversupply was 40 days. The cost of oversupply for exempt patients (i.e., patients who have paid 1,800 SEK (Euro 196; US$ 243) per year for medicines) was 32,000 SEK (Euro 3,500; US$ 4,300) higher than for non-exempt patients. An extrapolation to all Sweden indicates that exemption from charges leads to an additional oversupply of about 142 million SEK (Euro 15 million; US$ 19 million) per year above that of non-exempt patients. CONCLUSION: Both undersupply and oversupply of prescribed medicines are common in Sweden. Patients with a refill adherence below 80% seem to have less than half of the prescribed treatment available. Oversupply or drug stockpiling occurs more frequently among exempt than among non-exempt patients, and this oversupply leads to high unnecessary costs.
  •  
44.
  • Kälvemark Sporrong, Sofia, et al. (författare)
  • Challenges in qualitative social pharmacy research : Reflections based on a conference workshop
  • 2022
  • Ingår i: Research in Social and Administrative Pharmacy. - : Elsevier. - 1551-7411 .- 1934-8150. ; 18:1, s. 2254-2258
  • Tidskriftsartikel (refereegranskat)abstract
    • A methodological debate within social pharmacy is ongoing regarding how to apply a qualitative approach. This paper emanates from a workshop at the Nordic Social Pharmacy Conference in 2019, named 'How do we know it's good? A workshop on quality criteria in qualitative social and clinical pharmacy research', that addressed this debate. The aim of this paper is twofold (1) to present the main key points raised during the workshop and (2) based on these inputs to contribute to the ongoing discussion on qualitative methodology within social pharmacy research. This paper starts with what was discussed at the workshop and further elaborated are some of the challenges with conducting qualitative research within social pharmacy. These include methodological and disciplinary competence and insecurity, reflections on the consequences of that many social pharmacy researchers come from a natural science background and how this (possibly) shapes the practice of qualitative research within the field. For example, how concepts like transparency and saturation, together with checklists and quality criteria are understood and used. Finally, we make suggestions for the next step for qualitative research in social pharmacy.
  •  
45.
  • Lesén, Eva, 1982, et al. (författare)
  • Is the level of patient co-payment for medicines associated with refill adherence in Sweden?
  • 2014
  • Ingår i: European Journal of Public Health. - : Oxford University Press (OUP). - 1101-1262 .- 1464-360X. ; 24:1, s. 85-90
  • Tidskriftsartikel (refereegranskat)abstract
    • In the Swedish reimbursement scheme, the co-payment is based on the price of the product and decreases in a stepwise manner as the total accumulated co-payment increases. The aim of this study was to analyse how refill adherence in Sweden varies according to patient's co-payment level for medicines, with antiepileptic drug (AED) use as an example.
  •  
46.
  • Martínez, Clàudia Sabaté, et al. (författare)
  • Examination of the Protein Drug Supply Chain in a Swedish University Hospital : Focus on Handling Risks and Mitigation Measures
  • 2023
  • Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier. - 0022-3549 .- 1520-6017. ; 112:11, s. 2799-2810
  • Tidskriftsartikel (refereegranskat)abstract
    • Protein drugs, such as monoclonal antibodies, have proved successful in treating cancer and immune system diseases. The structural complexity of these molecules requires careful handling to ensure integrity and stability of the drug. In this study, a failure mode and effects analysis was performed based on a Gemba Walk method in a Swedish University Hospital. The Gemba Walk is focused on pharmacists observing the actual supply process steps from distributor, pharmacy cleanroom to patient administration. Relevant protein drugs are chosen based on sales statistics within the hospital and the corresponding wards were observed. Further is the Double Diamond design method used to identify major risks and deliver mitigation strategies. The study identified potential stress factors such as temperature, shock by impact, shaking, vibration and light exposure. There were also risks associated with porters’ and healthcare professionals’ lack of awareness and access to information. These risk factors may cause loss of efficacy and quality of the protein drug, potentially leading to patient safety concerns. In this study, a simulation is also performed to list measures that theoretically should be in place to ensure the quality of the protein drug, for example validated and protocol-based compounding in cleanroom, training and validated transports.
  •  
47.
  • Mårdby, Ann-Charlotte, 1976, et al. (författare)
  • Adherence to antidepressants among women and men described with trajectory models : a Swedish longitudinal study
  • 2016
  • Ingår i: European Journal of Clinical Pharmacology. - : Springer. - 0031-6970 .- 1432-1041. ; 72:11, s. 1381-1389
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of this study are to analyse adherence to antidepressant treatment over 2 years in Sweden among women and men who initiated treatment with citalopram and to identify groups at risk of non-adherence using trajectory models. The study population, including individuals 18-85 years who initiated citalopram use between 1 July 2006 and 30 June 2007, was identified in the Swedish Prescribed Drug Register and followed for 2 years. Adherence was estimated with continuous measure of medication acquisition (CMA) and group-based trajectory modelling, a method which describes adherence patterns over time by estimating trajectories of adherence and the individual's probability of belonging to a specific trajectory. The study population included 54,248 individuals, 64 % women. Mean CMA was 52 % among women and 50 % among men (p < 0.001). Five different adherence patterns (Trajectories) were identified. Similar proportion of women and men belonged to each Trajectory. Around 29 % of the women and 27 % of the men belonged to the Trajectory which showed full adherence throughout the 2-year study period. The other four Trajectories showed adherence that declined to different degrees and at different stages in time. Having low socioeconomic status was more common among individuals in Trajectories showing declining adherence than in the adherent Trajectory. Using trajectory modelling, five Trajectories describing different patterns of adherence to citalopram treatment over time were identified. A large proportion discontinued treatment early and having low socioeconomic status increased the risk of being non-adherent.
  •  
48.
  • Paulino Mendes, Ana Sofia, et al. (författare)
  • Outdoor environmental effects on cleanrooms – A study from a Swedish hospital pharmacy compounding unit
  • 2022
  • Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier. - 0939-6411 .- 1873-3441. ; 177, s. 100-106
  • Tidskriftsartikel (refereegranskat)abstract
    • In this study we examined how outdoor climate affects indoor conditions of a cleanroom used for the preparation of radiopharmaceuticals in the Uppsala university hospital pharmacy, Sweden. Further objectives were to identify associated risk factors to ensure a consistent extemporaneous manufacturing process. Data for two years from the facility monitoring system (with one minute resolution for temperature, relative humidity (%RH), differential pressure) were compared with meteorological outdoor data from Uppsala (Swedish Meteorological and Hydrological Institute, 60-minute mean data for temperature, relative humidity, wind speed and air pressure). The findings of this study indicate a linear relationship between indoor and outdoor temperature for the autumn, winter and spring seasons. The typical summer outdoor diurnal pattern is also seen for indoor temperature. During the study period, the minimum outdoor temperature was −17.5 °C and the maximum 31.4 °C. This wide temperature range also entails a wide range of air humidity from 10 %RH to 100 %RH indoors. Cleanroom temperature and %RH are factors that may affect the quality of medications, especially the risk of microbiological growth in aseptic processes, stability of medications during storage but also may affect handling of for example uncoated tablets or weighing of powder, especially at high %RH for hygroscopic drugs or at low %RH due to static electricity. Further the risk of damage on electrical equipment from electrostatic discharge at low %RH is discussed with a focus on the need for humidity control of cleanrooms and/or systems for mitigation of electrostatic discharge in climates with outdoor temperature in the wintertime below freezing point.
  •  
49.
  • Turanli, Beste Calimlioglu, et al. (författare)
  • Systems biology based drug repositioning for development of cancer therapy
  • 2021
  • Ingår i: Seminars in Cancer Biology. - : Elsevier BV. - 1096-3650 .- 1044-579X. ; 68, s. 47-58
  • Forskningsöversikt (refereegranskat)abstract
    • Drug repositioning is a powerful method that can assists the conventional drug discovery process by using existing drugs for treatment of a disease rather than its original indication. The first examples of repurposed drugs were discovered serendipitously, however data accumulated by high-throughput screenings and advancements in computational biology methods have paved the way for rational drug repositioning methods. As chemotherapeutic agents have notorious side effects that significantly reduce quality of life, drug repositioning promises repurposed noncancer drugs with little or tolerable adverse effects for cancer patients. Here, we review current drug-related data types and databases including some examples of web-based drug repositioning tools. Next, we describe systems biology approaches to be used in drug repositioning for effective cancer therapy. Finally, we highlight examples of mostly repurposed drugs for cancer treatment and provide an overview of future expectations in the field for development of effective treatment strategies.
  •  
50.
  • Wisell, Kristin, 1980-, et al. (författare)
  • The Raison D’être for the Community Pharmacy and the Community Pharmacist in Sweden: : A Qualitative Interview Study
  • 2016
  • Ingår i: Pharmacy. - : MDPI AG. - 2226-4787. ; 4:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Community pharmacies are balancing between business (selling medicines and other products) and healthcare (using the pharmacists’ knowledge in order to improve drug utilization). This balance could be affected by regulations decided upon by politicians, but also influenced by others. The aim of this study was to explore important stakeholders’ views on community pharmacy and community pharmacists in Sweden. The method used was that of semi-structured qualitative interviews. Political, professional, and patient organization representatives were interviewed.The results show that informants who are pharmacists or representatives of a professional pharmacist organization generally have a healthcare-centered view on community pharmacy/pharmacists. However, different views on how this orientation should be performed were revealed, ranging from being specialists to dealing with uncomplicated tasks. Political organization representatives generally had a more business-oriented view, where competition in the market was believed to be the main driving force for development. A third dimension in which competition was not stressed also emerged; that community pharmacies should primarily distribute medicines. This dimension was most prevalent among the political and patient organization representatives. One conclusion to be drawn is that no stakeholder seemed to have a clear vision or was willing to take the lead for the development of the community pharmacy sector.
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